UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The iv administration of soman (25 micrograms/kg) resulted in inhibition of cholinesterase activity in plasma, brain, and diaphragm, as well as depression of spontaneous activity and rectal temperature in mice. The motor activity and rectal temperature of these animals had returned to control levels within 24 hr, but cholinesterase activity was not fully recovered after 3 days. Following iv administration of [3H]soman (25 micrograms/kg), only trace quantities of [3H]soman were found in all tissues as early as 1 min after injection. Almost half of the injected material was present in the form of free [3H]pinacolylmethylphosphoric acid (PMPA) within 1 min of injection of [3H]soman. The concentrations of [3H]PMPA fell by more than 50% by 1 hr. High concentrations of covalently bound [3H]PMPA were present in all tissues immediately after [3H]soman treatment, particularly in lungs, heart, and kidneys. These concentrations declined slowly and after 8 hr, the quantities of bound [3H]PMPA in most tissues had fallen by less than 50%. The radioactivity in brain was identified as bound and free [3H]PMPA, nonextractable radioactivity (presumably [3H]methylphosphonic acid), and only traces of [3H]soman. It appears that phosphorylation of cholinesterase in the central nervous system is not solely responsible for depression of motor activity and rectal temperature.
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PMID:Relationship between the biodisposition of [3H]soman and its pharmacological effects in mice. 403 96

The lethality of organophosphate (OP) cholinesterase (CHE) inhibitors is thought to result from depression of the respiratory center in the brain stem, constriction of and increased secretion by the airways, and paralysis of the respiratory musculature. While tolerance to the cholinergic toxicity of OPs has been well documented, such studies have not included investigations of the brain stem and extrapulmonary airways. In this report tolerance to the insecticide malathion is demonstrated. At 24 hr after 14 daily doses of malathion (400 mg/kg, ip), CHE activities were 27, 26, and 28% of control in striatum (ST), hippocampus (HI), and cortex (CX), respectively, while brain stem CHE activity was 41% of control. In addition, the numbers of muscarinic receptors (Bmax) decreased 30, 20, and 22% in ST, HI, and CX, respectively. In contrast, there was no change in brain stem Bmax. The lack of parallelism between CHE inhibition and Bmax effects in brain stem as compared to all other tissues tested raises questions as to the mechanism(s) by which the respiratory system adapts during repeated OP exposure.
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PMID:Differential cholinesterase inhibition and muscarinic receptor changes in CD-1 mice made tolerant to malathion. 404 16

Clinically normal Nubian goats were given the antiprotozoal drug imidocarb at single intramuscular doses of 6, 12, 18 and 24 mg/kg, and the various clinical, biochemical and pathological manifestations were recorded. At a dose of 6 mg/kg the drug produced no change in any of the parameters studied. At higher doses, the drug produced dose dependent changes which included increased heart and respiratory rates, increased defaecation, urination, depression, incoordination of movement, weakness of the hindlegs, recumbency, and finally death. Just prior to death, there was a significant decrease in the number of erythrocytes, and in packed cell volume, and haemoglobin concentration. In plasma there was an increase in the activity of aspartate transaminase, urea and creatinine concentrations and inhibition of cholinesterase activity. The main histopathological changes were associated with hepatic and renal damage. Three goats were pre-treated with atropine sulphate (1 mg/animal) and after one hour given imidocarb intramuscularly at a dose of 12 mg/kg. The changes were similar but much less severe when compared with those in animals given imidocarb alone at the same dose.
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PMID:Some effects of imidocarb in goats. 408 55

The neuromuscular junctions from diaphragm, soleus, and extensor digitorum longus (EDL) muscles of male albino rats were assessed for morphological alterations following acute (30-min) and subacute (2-day) exposure to pyridostigmine bromide in Mestinon-equivalent buffer. These muscles were selected to compare the effects of the drug on muscles of different fiber type composition. The diaphragm has approximately equal numbers of type I and type II fibers while the soleus and EDL possess primarily type I and type II fibers, respectively. Pyridostigmine was administered to each acute-exposure animal by a single subcutaneous injection of 0.36 mg/kg pyridostigmine and to each subacute-exposure animal by a subcutaneously implanted osmotic minipump containing 10 mg/ml pyridostigmine. Both treatments resulted in whole blood cholinesterase (ChE) depression of approximately 60-70% as determined by radiometric assay. Control animals received only Mestinon-equivalent buffer. Both acute and subacute exposures resulted in morphological alteration of the neuromuscular junctions (NMJs) of all three muscles, although considerable variation in the extent of damage occurred even within individual NMJs. The most frequently observed presynaptic alterations were mitochondrial damage and partial withdrawal of nerve terminal branches (partial denervation). Post-synaptic changes included occasional rarefaction of mitochondrial matrices and disruption of the myofibrillar organization in small numbers of subjunctional sarcomeres. The data indicate that acute or subacute exposure to pyridostigmine bromide at a whole blood ChE depression of 60-70% results in similar alterations to the NMJs of three muscles with substantially different fiber type compositions. Although the severity of the damage varies from fiber to fiber, the variability appears random and not related to a specific fiber type or dosage regimen.
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PMID:Neuromuscular toxicity of pyridostigmine bromide in the diaphragm, extensor digitorum longus, and soleus muscles of the rat. 409 93

1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O(2) in N(2)) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve.2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4.0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H(+) ions probably acted as membrane ;stabilizers' without depolarizing either the nerve fibres or endings.3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 mug) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh.4. Choline chloride (10(-3)M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10(-5)M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh.5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca(2+), acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca(2+) concentration was raised, but their effects declined as Ca(2+) was increased above normal values. Mg(2+) ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg(2+) was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption.6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-beta-erithroidine (DHE), HC-3 (10(-4)M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE.7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid.8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968).
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PMID:Pharmacology of pH effects on carotid body chemoreceptors in vitro. 429 75

1. Studies involving the electrophoretic administration of antagonists of ACh (atropine, DHbetaE) and cholinesterase inhibitors (neostigmine, physostigmine) to MGN neurones indicate that ACh is an excitatory transmitter in the feline MGN, most probably released from fibres which originate in or traverse the mesencephalon.2. Auditory afferents to the MGN, cortico-geniculate fibres and the excitatory fibres which mediate ;spontaneous' firing of MGN neurones are unlikely to be cholinergic.3. Almost all geniculo-cortical relay cells are excited by ACh, this excitation being mediated by receptors which have both muscarinic and nicotinic properties. The excitation of relay cells by ACh is sometimes preceded or followed by a depression of firing which is resistant to atropine and DHbetaE, but the significance of this depression is unknown.4. The firing of many unidentified MGN neurones is depressed by ACh in the absence of any excitation, and this depression is blocked by both atropine and DHbetaE, and potentiated by anticholinesterases. This type of depression by ACh may be related to cholinergic inhibition, but this possibility has yet to be investigated.
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PMID:Cholinergic and non-cholinergic transmission in the medial geniculate nucleus of the cat. 434 15

1. A study has been made of the formation of synapses in spontaneously reinnervated and cross-reinnervated anterior latissimus dorsi (ALD) and posterior latissimus dorsi (PLD) muscles of adult fowls.2. Denervated ALD and PLD muscle fibres have a uniform and high sensitivity to iontophoretically applied acetylcholine (ACh). During early reinnervation the sensitivity distribution to ACh of the ALD muscle fibres begins to return to normal before synaptic potentials can be evoked. The normal ACh sensitivity distribution of PLD muscle fibres is also restored after reinnervation. After cross-reinnervation of the ALD and PLD muscles the ACh sensitivity distribution of many of the muscle fibres is again restored to normal.3. Reinnervating and cross-reinnervating ALD nerve terminals showed a greater than normal degree of facilitation of transmitter release when a test impulse was applied at various intervals after a conditioning impulse. Cross-reinnervating PLD nerve terminals showed facilitation of transmitter release rather than the normal depression in a conditioning-test impulse sequence.4. The distribution of nerve terminals over the surface of spontaneously reinnervated and cross-reinnervated ALD and PLD muscle fibres has been determined from an examination of the sensitivity distribution to applied ACh, the graded versus all-or-none nature of the evoked potential and the distribution of cholinesterase stained synapses.5. The results suggest that the innervation pattern of individual ALD and PLD muscle fibres is restored both after spontaneous reinnervation and cross-reinnervation.
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PMID:The formation of synapses in reinnervated and cross-reinnervated adult avian muscle. 435 Jul 69

1. Oxygen consumption in vitro and persistence in the general circulation of rabbit erythrocytes treated with the cholinesterase inhibitor paraoxon were determined.2. Paraoxon in vitro reduced oxygen consumption below a measureable level within 2 hours. By contrast, the metabolic inhibitor N-ethylmaleimide (NEM) produced complete inhibition within 15 minutes.3. Erythrocytes from rabbits orally dosed with parathion also exhibited marked depression of oxygen consumption.4. Glutathione (GSH) restored oxygen uptake to pretreatment levels within 15 min in erythrocytes previously inhibited with NEM or paraoxon.5. Erythrocytes treated with NEM were rapidly removed from the general circulation while paraoxon treated cells were removed at a rate comparable to untreated cells.
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PMID:Effect of paraoxon on erythrocyte metabolism as measured by oxygen uptake in vitro. 509 Nov 62

1. Acetylcholine (ACh), other cholinomimetics, cholinesterase inhibitors and cholinergic antagonists were administered iontophoretically to medial geniculate (MG) neurones and their effects on chemically or neurally evoked responses recorded extracellularly.2. Acetylcholine had excitant actions on 45% of the neurones tested. Most of these were of a slow time course. Desensitization to the excitant effects was frequently observed.3. Acetylcholine excited 91% of neurones activated antidromically by stimulation of the auditory cortex, 71% of neurones activated synaptically from the auditory cortex, 74% of neurones activated from the inferior colliculus and 100% of geniculo-cortical relay neurones.4. Acetylcholine had depressant effects, which were generally of a rapid time course, on 29% of MG neurones. No desensitization to the depressant effects was observed.5. On 4% of neurones, ACh had both excitant and depressant effects. Such "dual" effects were manifested either as an initial excitation followed by a depression, or as a depression followed by an excitation.6. Eserine, neostigmine and edrophonium potentiated both excitant and depressant actions of ACh on many cells. Neostigmine and edrophonium occasionally antagonized the effects of ACh.7. Atropine, hyoscine, dihydro-beta-erythroidine, hexamethonium and (+)-tubocurarine antagonized both excitant and depressant effects of ACh. The muscarinic blocking agents were usually more effective than the nicotinic agents.8. Carbamylcholine, acetyl-beta-methylcholine, nicotine, butyrylcholine, arecoline and pilocarpine had excitant, depressant or no effects on MG neurones. Generally, carbamylcholine was more potent than acetyl-beta-methylcholine and ACh, which were more potent than nicotine. Butyrylcholine, arecoline and pilocarpine were even less potent, often having no effect.9. The cholinomimetics generally had similar effects to those of ACh on the same neurones, but sometimes were quite different. Carbamylcholine, acetyl-beta-methylcholine and nicotine antagonized the effects of ACh on some neurones.10. The results suggest that cholinoceptive receptors on MG neurones are not homogeneous. Although there are possibly some purely muscarinic and purely nicotinic receptors, the majority appear to be of intermediate muscarinic-nicotinic type. These mediate either excitation or inhibition.
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PMID:Properties of cholinoceptive neurones in the medial geniculate nucleus. 541 82

Actions of the two cholinesterase inhibitors: armin and galanthaamine on the neuromuscular transmission and on the spontaneous and evoked acetylcholine release were studied in the rat diaphragm. High concentrations (greater than or equal to 10(-6) g/ml) of these agents exhausted the available transmitter store which decreased the quantum content of e. p. p. sin single nerve stimulation. At the repetitive stimulation (10-100 s-1), armin and galanthaamine accelerated the presynaptic depression of e. p. p. s and slowed down the rate of transmitter mobilization. This resulted in a rapid decrease of quantum content and amplitude of e. p. p. s. The found presynaptic deteriorations together with the stationary postsynaptic depolarization may cause the neuromuscular block.
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PMID:[Presynaptic action of armin and galantamin on mammalian neuromuscular junction]. 609 74

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