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Biomedical subjects

B Collier

Publications and source records attributed to B Collier.

At least 73 records · Page 4Linked to original sources
PubMed1989

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

Aged↗
PubMed1989

Nutritional factors in diabetics with and without retinopathy.

We used 3-d food-record-keeping techniques to examine nutritional factors in diabetic patients with and without retinopathy. Patients without retinopathy had significantly higher daily intakes of total carbohydrate, water-soluble dietary fibers, insoluble dietary fibers, and glucose than did patients with retinopathy. Also, patients without retinopathy took a significantly lower proportion of their total daily calories as protein.

Adult↗
PubMed1989

Acetylcholine synthesis by a sympathetic ganglion in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and picrylsulfonic acid.

The present experiments measured the release and the synthesis of acetylcholine (ACh) by cat sympathetic ganglia in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183 or vesamicol) and/or picrylsulfonic acid (TNBS), two compounds known to have the ability to block the uptake of ACh by cholinergic synaptic vesicles in vitro. We confirmed that, in stimulated (5 Hz) perfused (30 min) ganglia, AH5183 depressed ACh release and ACh tissue content increased by 86 +/- 6% compared to contralateral ganglia used as controls. Preganglionic activity increased ACh release by a similar amount in the presence (19.9 +/- 1.0 pmol/min) or absence (20.5 +/- 2.4 pmol/min) of TNBS. The final tissue ACh content was also similar in the presence (1,668 +/- 166 pmol) or absence (1,680 +/- 56 pmol) of TNBS. However, the AH5183-induced increase of tissue ACh content (86 +/- 6%) was abolished completely when AH5183 was perfused with 1.5 mM TNBS (-3.0 +/- 1.0%). This inhibition of ACh synthesis, observed in TNBS-AH5183-perfused ganglia, was not dependent upon further inhibition of ACh release beyond that caused by AH5183 alone, because 14.0 +/- 1.9% of the transmitter store was released by preganglionic nerve stimulation in the presence of TNBS plus AH5183 and this was similar in the presence of AH5183 without TNBS (14.0 +/- 0.6%). Moreover, when ganglia were first treated with TNBS and then stimulated in the presence of AH5183, an increase of 64 +/- 6% of the ganglionic ACh content occurred, and this increase was not statistically different from the increase measured with AH5183 alone (86 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Effect of chronic nicotine treatment on nicotinic autoreceptor function and N-[3H]methylcarbamylcholine binding sites in the rat brain.

It has been reported that N-methylcarbamylcholine (MCC), a nicotinic agonist, binds to central nicotinic receptors and causes an increase of acetylcholine (ACh) release from certain central cholinergic nerve terminals. The present experiments determine whether these two phenomena change in response to the chronic administration of nicotine, a procedure known to result in an increase in nicotinic binding sites. Chronic nicotine caused a brain region-specific up-regulation of [3H]MCC sites; binding increased in the frontal cortex, parietal cortex, striatum, and hippocampus, but not in the occipital cortex or cerebellum. The effect of nicotine was selective to nicotinic binding sites, because muscarinic sites, both M1 ([ 3H]pirenzepine) and M2 ([3H]ACh), were unaffected by chronic nicotine treatment. MCC increased the release of ACh from the frontal cortex and hippocampus by a calcium-dependent mechanism; MCC did not alter ACh release from striatum or occipital cortex of control animals. The MCC-induced increase in ACh release was not apparent in those animals which had been treated with nicotine. There was a partial recovery of nicotinic autoreceptor function when animals were allowed to recover (4 days) following chronic nicotine treatment, but the density of binding sites remained increased compared to control. Chronic nicotine did not change the potassium-evoked release of ACh from the frontal cortex or hippocampus, but decreased this measure from striatum. It also decreased the ACh content of the striatum, but not that of the cortex or the hippocampus; the activity of choline acetyltransferase was not altered in any of the regions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Presynaptic cholinergic mechanisms in the rat cerebellum: evidence for nicotinic, but not muscarinic autoreceptors.

The present study shows that N-[3H]methylcarbamylcholine ([3H]MCC) binds to a single population of high-affinity/low-density (KD = 5.0 nM; Bmax = 8.2 fmol/mg of protein) nicotinic binding sites in the rat cerebellum. Also, there exists a single class of high-affinity binding sites (KD = 4.8 nM; Bmax = 24.2 fmol/mg of protein) in the cerebellum for the M1 specific muscarinic ligand [3H]pirenzepine. In contrast, the M2 ligand, [3H]AF-DX 116, appears to bind to two classes of binding sites, i.e., a high-affinity (KD = 3 nM)/low-capacity (Bmax = 11.7 fmol/mg of protein) class, and a second class of lower affinity (KD = 28.4 nM) and higher capacity (Bmax = 36.3 fmol/mg of protein) sites. The putative M3 selective ligand [3H]4-diphenylacetoxy-N-methylpiperidine also binds to two distinct classes of binding sites in cerebellar homogenates, one of high affinity (KD = 0.5 nM)/low capacity (Bmax = 19.5 fmol/mg of protein) and one of low affinity (KD = 57.5 nM)/high capacity (Bmax = 140.6 fmol/mg of protein). In experiments which tested the effects of cholinergic drugs on acetylcholine release from cerebellar brain slices, the nicotinic agonist MCC enhanced spontaneous acetylcholine release in a concentration-dependent manner, and the maximal increase in acetylcholine release (59.0-68.0%) occurred at 10(-7) M. The effect of MCC to increase acetylcholine release was Ca2+-dependent and tetrodotoxin-insensitive, suggesting an action on cholinergic terminals. Also, the MCC-induced increase in acetylcholine release was effectively antagonized by dihydro-beta-erythroidine, d-tubocurarine, and kappa-bungarotoxin, but was insensitive to either atropine or alpha-bungarotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Retinal leakage in retinal vein occlusion: reduction after hyperbaric oxygen.

A 54-year-old woman with a history of bilateral central retinal vein occlusion, probably due to an inflammatory process, developed a hemispheric retinal vein occlusion with cystoid macular edema in her only seeing eye. Five months later, in the absence of improvement in vision and macular edema, she received on two occasions a 2-weekly course of twice daily 100% hyperbaric oxygen. After each course retinal leakage, as assessed by vitreous fluorophotometry, decreased from abnormal to the normal range while visual acuity improved by two lines. The possible implications are discussed.

Female↗
PubMed1988

Influx of a choline analog to dog brain measured by positron emission tomography.

The influx of the 11C-labeled choline analog pyrrolidinocholine into tissue was measured in the brain of three dogs by positron emission tomography (PET). During the first 90 s after the intravenous bolus injection of the tracer, transfer of tracer from plasma to tissue was unidirectional. The influx constant for pyrrolidinocholine into intracranial tissue, Kin, was 0.017 ml/g/min (0.008 SD), and the initial volume of distribution, V0, was 0.08 ml/g (0.03 SD). The influx constant was at least five times larger than the value expected if simple diffusion were to account for tissue uptake. The method presented in this paper can be used to investigate the availability of plasma choline and its analogs to the living human brain and other tissue in degenerative diseases affecting the cholinergic system, and to provide in vivo information on a choline transport system.

Animals↗
PubMed1988

Characterization of N-[3H]methylcarbamylcholine binding sites and effect of N-methylcarbamylcholine on acetylcholine release in rat brain.

The present experiments show that N-[3H]-methylcarbamylcholine ([3H]MCC) binds specifically and with high affinity to rat hippocampus, frontal cortex, and striatum. The highest maximal density of binding sites was apparent in frontal cortex and the lowest in hippocampus. [3H]MCC binding was potently inhibited by nicotinic, but not muscarinic, agonists and by the nicotinic antagonist dihydro-beta-erythroidine in all three brain regions studied. The effect of unlabeled MCC on acetylcholine (ACh) release from slices of rat brain was tested. The drug significantly enhanced spontaneous ACh release from slices of hippocampus and frontal cortex, but not from striatal slices. This effect of MCC to increase ACh release from rat hippocampus and frontal cortex was antagonized by the nicotinic antagonists dihydro-beta-erythroidine and d-tubocurarine, but not by alpha-bungarotoxin or by the muscarinic antagonist atropine. The MCC-induced increase in spontaneous ACh release from hippocampal and frontal cortical slices was not affected by tetrodotoxin. The results suggest that MCC might alter cholinergic transmission in rat brain by a direct activation of presynaptic nicotinic receptors on the cholinergic terminals. That this alteration of ACh release is apparent in hippocampus and frontal cortex, but not in striatum, suggests that there may be a regional specificity in the regulation of ACh by nicotinic receptors in rat brain.

Acetylcholine↗
PubMed1988

Arachidonic acid inhibits choline uptake and depletes acetylcholine content in rat cerebral cortical synaptosomes.

The effects of arachidonic acid on [3H]choline uptake, on [3H]acetylcholine accumulation, and on endogenous acetylcholine content and release in rat cerebral cortical synaptosomes were investigated. Arachidonic acid (10-150 microM) produced a dose-dependent inhibition of high-affinity [3H]choline uptake. Low-affinity [3H]choline uptake was also inhibited by arachidonic acid. Fatty acids inhibited high-affinity [3H]choline uptake with the following order of potency: arachidonic greater than palmitoleic greater than oleic greater than lauric; stearic acid (up to 150 microM) had no effect. Inhibition of [3H]choline uptake by arachidonic acid was reversed by bovine serum albumin. In the presence of arachidonic acid, there was an increased accumulation of choline in the medium, but this did not account for the inhibition of [3H]choline uptake produced by the fatty acid. Arachidonic acid inhibited the synthesis of [3H]acetylcholine from [3H]choline, and this inhibition was equal in magnitude to the inhibition of high-affinity [3H]choline uptake produced by the fatty acid. A K+-stimulated increase in [3H]acetylcholine synthesis was inhibited completely by arachidonic acid. Arachidonic acid also depleted endogenous acetylcholine stores. Concentrations of arachidonic acid and hemicholinium-3 that produced equivalent inhibition of [3H]choline uptake also produced equivalent depletion of acetylcholine content. In the presence of eserine, arachidonic acid had no effect on acetylcholine release. The results suggest that arachidonic acid may deplete acetylcholine content by inhibiting high-affinity choline uptake and subsequent acetylcholine synthesis. This raises the possibility that arachidonic acid may play a role in the impairment of cholinergic transmission seen in cerebral ischemia and other conditions in which large amounts of the free fatty acid are released in brain.

Acetylcholine↗
PubMed1988

Vasoactive intestinal peptide increases acetylcholine synthesis by rat hippocampal slices.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) might have a presynaptic modulatory effect at cholinergic terminals in the rat hippocampal formation. The exposure of rat hippocampal slices to VIP increased [3H]acetylcholine ([3H]ACh) synthesis from the precursor [3H]choline when tissue was incubated in normal or in high K+ medium; the maximal effect was apparent at 10(-8) M VIP and 10(-7) M VIP, respectively. Also, 10(-7) M VIP increased the activity of choline acetyltransferase (ChAT) in a hippocampal homogenate system. The increased synthesis by hippocampal slices was not the result of a VIP-induced alteration in either the basal release of ACh or the uptake of choline via the high-affinity uptake system. The increase in ACh synthesis induced by VIP in hippocampal slices was not associated with either adenylate cyclase or protein kinase C second messenger systems. There was no correlation between the effect of VIP on cyclic AMP production with that on ACh synthesis; also, forskolin, an activator of adenylate cyclase that increased cyclic AMP production 3.5-fold, did not mimic the effect of VIP on ACh synthesis. Similarly, there was no effect of the protein kinase C activator, phorbol myristate acetate, on ACh synthesis in hippocampal slices. However, the effect of VIP to increase ACh synthesis was not evident in the absence of extracellular calcium, suggesting that the effect of VIP is mediated by a calcium-requiring mechanism. The results suggest that, in the rat hippocampus, VIP has a presynaptic action at cholinergic terminals that results in enhanced synthesis of ACh, possibly by an action that alters ChAT activity.

Acetylcholine↗
PubMed1988

Acetylcholine mobilization in a sympathetic ganglion in the presence and absence of 2-(4-phenylpiperidino)cyclohexanol (AH5183).

The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2-(4-phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13-14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recovery from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183-treated ganglia, as determined by the synthesis of [3H]ACh from [3H]choline, and this [3H]ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh, and thus we conclude that ACh synthesized in the presence of AH5183 is a releasable as pre-existing ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with [3H]choline) and that synthesized during recovery from the drug's effects (perfusion with [14C]choline: the ratio of [3H]ACh to [14C]ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183-induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183-blocked ganglia, even in the drug's continued presence. Venom-induced release of ACh from AH5183-treated ganglia was not less than the venom-induced release from tissues not exposed to AH5183. This effect of BWSV was attributed to the action of the protein, alpha-latrotoxin, because an anti-alpha-latrotoxin antiserum blocked the venom's action. ACh synthesized during AH5183 exposure was labelled from [3H]choline, and subsequent treatment with BWSV released [3H]ACh with the same temporal pattern as the release of total ACh. To exclude a nonexocytotic origin for the [3H]ACh released by BWSV, ganglia were preloaded with [3H]diethylhomocholine to form [3H]acetyldiethylhomocholine, an ACh analogue excluded from vesicles; the venom did not increase the rate of [3H]acetyldiethylhomocholine efflux. It is concluded that a vesicular ACh pool insensitive to the inhibitory action of AH5183 might exist and that this vesicular pool is not mobilized by electrical stimulation to exocytose in the presence of AH5183, but it is by BWSV.

Acetylcholine↗
PubMed1988

An electron microscopic study of hemopoietic tissues in the course of Lewis lung carcinoma.

Lewis lung carcinoma of C57Bl/6 mice causes a progressive anemia with reticulocytosis and splenomegaly, metastasizes to lungs, liver, and kidneys but does not invade hemopoietic tissues. The cause of this anemia is uncertain. We studied the structure of spleen and bone marrow in these tumor hosts by light and electron microscopy. Splenic congestion of the red pulp with numerous erythropoietic islands and marrow hyperplasia characterized the hemopoietic tissues of these mice, which, when coupled with other hematological parameters suggested a hemolytic condition. However, the erythropoietic response appeared to be in part ineffective as evidenced by phagocytosis of immature as well as mature red blood cells within the spleen and marrow. Thus, the condition of anemia in Lewis lung carcinoma may result from a multifactorial response of hemolysis and ineffective erythropoiesis and hemolysis.

Anemia↗
PubMed1988

Cytoskeletal organization of a cloned hemopoietic stromal cell line during attachment and spreading.

The cell membrane of a cloned murine bone marrow stromal cell line D2XRII was extracted in situ using Triton X-100 detergent and the cytoskeletal structure studied during the process of adherence and spreading. During this process, three zones can be identified in the cytoplasm: the perinuclear zone, which was the fixed part of the cell; the peripheral mixed filamentous zone, which formed the core of long cytoplasmic projections; and an outer zone, which formed the boundary of cytoplasmic projections and contained only intermediate filaments. The process of spreading appeared to originate from very long strips of microfilaments emanating from the second zone, crossing the width of the outer zone, and extending beyond for a long distance. The second and third zones then appeared to "stream out" around the axis of this strip, and in this fashion the cytoplasm spreads over the substratum.

Animals↗
PubMed1987

Do presynaptic opiate receptors and alpha-adrenoceptors alter acetylcholine release from a sympathetic ganglion by a similar mechanism?

The present experiments tested the possible involvement of a calcium-sensitive mechanism in the alpha-adrenoceptor- and opiate receptor-mediated inhibition of acetylcholine release from the cat superior cervical ganglion. First, the calcium-dependence of evoked acetylcholine release was measured in the presence and absence of the alpha-adrenoceptor agonist noradrenaline or of the opiate receptor agonist [Met5]enkephalin-Arg6-Phe7. When ganglia were perfused with Krebs medium containing [Ca2+] = 2.4, 1.2, 0.6, 0.2 mM, evoked release of acetylcholine was depressed by both agonists and the inhibition increased with reduced levels of extracellular Ca2+; this was especially evident when calcium in the medium was reduced to 0.2 mM. Second, the effects of both noradrenaline and [Met5]enkephalin-Arg6-Phe7 on calcium influx into presynaptic nerve endings was determined by measuring the accumulation of 45Ca into ganglia in the presence and absence of either drug. Both agonists reduced the stimulation-induced increase in 45Ca accumulation. The effect of noradrenaline to reduce calcium influx was blocked by yohimbine or by phentolamine; the effect of [Met5]enkephalin-Arg6-Phe7 to decrease 45Ca accumulation by ganglia was blocked by naloxone. It is concluded that activation of presynaptic opiate receptors and alpha-adrenoceptors in the cat superior cervical ganglion can alter acetylcholine release by a similar mechanism, i.e. to reduce Ca2+ influx during preganglionic nerve stimulation.

Acetylcholine↗
PubMed1987

Apamin and nonadrenergic inhibition of guinea pig trachealis.

Apamin has been shown to antagonize the nonadrenergic, noncholinergic (NANC) inhibitory system in guinea pig taenia coli. We have examined the effects of apamin on the nonadrenergic noncholinergic inhibitory system and its putative transmitters in isolated guinea pig trachea. Electrical field stimulation (ES) of isolated trachea pretreated with atropine and propranolol evoked reproducible relaxations that were blocked by tetrodoxin, but were unaffected by apamin. Vasoactive intestinal peptide (VIP), adenosine (AD), and adenosine triphosphate (ATP) produced concentration-dependent inhibition of histamine (H)-induced contractions of isolated trachea but the inhibitory actions of these agents were not significantly affected by apamin. In contrast, apamin virtually abolished ES-evoked relaxations in guinea pig isolated taenia caeci, and reduced the inhibition of H-induced contraction by ATP from 40% to 1%. We conclude that neither the NANC inhibitory system in the guinea pig trachea nor its putative mediators VIP, AD, and ATP are antagonized by apamin, in contrast to taenia caeci.

Adenosine↗
PubMed1987

Target organ destruction enhances recovery of choline acetyltransferase activity in adult rat sympathetic ganglia after denervation.

We studied the effect of destruction of the adrenergic neuronal population on the recovery of preganglionic choline acetyltransferase activity in adult rat sympathetic ganglia. To produce a partial destruction of the adrenergic system, rats were injected with guanethidine for 4 weeks; the preganglionic nerve to the superior cervical ganglion was then crushed and the guanethidine injections were continued for an additional 3 days to 6 weeks. To determine that the drug was effective, tyrosine hydroxylase activity was assessed; enzymic activity was reduced by 76% or more after guanethidine administration. In addition, electron microscopy studies showed that the number of principal cell-synaptic contacts and vesicle-containing varicosities were decreased by 90% after guanethidine administration. Those measures indicated the drug effectively destroyed the postsynaptic adrenergic neurons. In contrast, crushing the preganglionic nerve in animals not treated with guanethidine did not change tyrosine hydroxylase activity, suggesting minimal nonspecific damage to the ganglion as a result of the lesion. Choline acetyltransferase activity was measured as an index of presynaptic cholinergic integrity. After crush of the preganglionic nerve, there was a gradual recovery of ganglionic choline acetyltransferase activity in the saline-injected rats from 5% of control 3 days after the crush to 49% of control after 6 weeks. On the other hand, in the ganglia of rats administered guanethidine, there was a much enhanced recovery of choline acetyltransferase activity after the nerve crush compared with saline-injected animals; in the guanethidine-injected rats, the ganglionic choline acetyltransferase activity 3 days and 6 weeks after the nerve crush was 15 and 96%, respectively, compared with the uncrushed side. These results demonstrate after destruction of the adrenergic target tissue, recovery of presynaptic choline acetyltransferase activity in the adult rat sympathetic ganglion can still occur after denervation; however, the mechanism(s) that controls the regeneration is altered, so that enzymic activity is enhanced.

Animals↗
PubMed1987

Effect of endogenous prostaglandins on acetylcholine release from dog trachealis muscle.

We used a radioenzymatic technique to measure effects of the prostaglandin synthesis inhibitor indomethacin and of exogenous prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) on acetylcholine (ACh) efflux from canine tracheal smooth muscle (TSM) during sustained electrical field stimulation (EFS; 2 Hz, 2 ms pulse duration, 50 V for 15 min). ACh efflux from indomethacin (INDO, 10(-6) M)-pretreated and control TSM increased with consecutive stimulations. However, efflux of ACh was greater in INDO-treated than control muscles. INDO increased the tension produced by TSM in response to EFS. Neither PGE2 (10(-8) M) nor PGI2 (10(-6) M) had any effect on ACh efflux from INDO-pretreated TSM during the first of three periods of EFS. However, PGI2 and PGE2 prevented the progressive increase in ACh efflux observed on subsequent stimulations. PGE2 but not PGI2 decreased contractions of TSM caused by EFS. Our results demonstrate that endogenous prostaglandins, probably PGE2, do inhibit EFS-evoked ACh release from canine TSM in vitro, but suggest that these prostaglandins modulate EFS-evoked contractions predominantly by postsynaptic mechanisms.

Acetylcholine↗