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Biomedical subjects

J G Clement

Publications and source records attributed to J G Clement.

At least 91 records · Page 5Linked to original sources
PubMed1982

HI-6: reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat.

HI-6, ([[[(4-aminocarbonyl)pyridino]methoxy]methyl]-2-] (hydroxyimino)methyl]-pyridinium dichloride), is an oxime which, when combined with atropine, is an extremely effective therapy against organophosphate poisoning. It was found that, following soman (287 micrograms/kg) poisoning, HI-6 reactivated acetylcholinesterase in the diaphragm and intercostal muscles but not in the brain. At a lower dose of soman (110 micrograms/kg), HI-6 reactivated sarin-inhibited acetylcholinesterase in the brain and in the respiratory musculature but did not reactivate tabun-inhibited acetylcholinesterase. It was also found that soman produced a differential inhibition of diaphragm and intercostal muscle acetylcholinesterase in vivo, whereas the in vitro I50 for soman was the same in both areas. HI-6 was capable of reactivating soman-inhibited acetylcholinesterase when administered up to 30 min post-soman, indicating that the rate of aging of the soman-acetylcholinesterase complex is slower than previously reported. The above results suggest that, in severe soman poisoning, the primary lesion occurs in peripheral acetylcholinesterase in the respiratory musculature (specifically the diaphragm).

Acetylcholinesterase↗
PubMed1981

BaCl2-induced contractions in the guinea pig ileum longitudinal muscle: role of presynaptic release of neurotransmitters and Ca2+ translocation in the postsynaptic membrane.

Early studies indicated that the baCl2-induced contractions in the guinea pig ileum longitudinal muscle strip (GPI-LMS) were, in part, neuronal in origin. However, recent studies have suggested that BaCl2-induced contractions were produced by an action directly on the smooth muscle membrane. The purpose of this study was to investigate the mechanism of the BaCl2 contractions in the GPI-LMS. Botulinum toxin (5 x 10(5) MLD/mL), which blocks the electrically induced release of acetylcholine (ACh), hemicholinium-3 (HC-3; 110 micro M), which blocks ACh synthesis, tetrodotoxin (TTX; 60 nM), which blocks Na+ channels, black widow spider venom, which depletes the presynaptic neuron of neurotransmitter, and atropine (2.9 micro M), a potent muscarinic antagonist, had no effect on the BaCl2 contractions. Densensitization of the GPI-LMS to substance P did not affect the BaCl2 contraction. In Ca2+ -free buffer the BaCl2 dose-response curve was shifted to the right. In Ca2+-free solution the time to 50% inhibiton of the contractile response to ACh (73 nM) and BaCl2 (1.16 mM) was 3.7 and 125 min, respectively. The D 600 Ic50 for ACh and BaCl2 contractions was 220 and 130 nM, respectively. In Ca2+-free buffer either EGTA (0.53 mM) or D 600 (1 micro M) were potent inhibitors of BaCl2 contractions. These results suggest that in the GPI-LMS the BaCl2 response is not mediated by a release of ACh (or substance P) because inhibitors of ACh release, synthesis, and receptors do not affect the responses. Also, the BaCl2 contraction is not due to activation of Na+ channels because TTX is without effect. The BaCl2-induced contraction appears to be mainly due to the movement of membrane bound Ca2+ through D 600 sensitive Ca2+ channels with extracellular Ca2+ and possible passage of Ba2+ ions intracellularly playing relatively minor roles.

Animals↗
PubMed1981

Methylxanthines antagonize adenosine but not morphine inhibition in guinea pig ileum.

In the electrically stimulated guinea pig ileum longitudinal muscle strip preparation the inhibitory actions of adenosine were antagonized by various concentrations of theophylline (12.5 and 100 micro M) and 8-phenyltheophylline (4 and 20 micro M). However, the inhibitory actions of morphine were not antagonized by the same concentration of theophylline and 8-phenyltheophylline. These results suggest that in the guinea pig ileum longitudinal muscle-strip adenosine is not a mediator in the inhibitory actions of morphine.

Adenosine↗
PubMed1980

Ethanol potentiation of choline, acetylcholine, carbachol and phenyltrimethylammonium contractions in the chick biventer cervicis muscle.

Pretreatment of chick biventer cervicis preparations with ethanol (290 mM) potentiated the EC50 of choline, acetylcholine, carbachol and phenyltrimethylammonium 91%, 319%, 97% and 213%, respectively. Perhaps this interaction of ethanol and neurotransmitter could contribute to the effects on coordination and motor activity produced by ethanol in vivo.

Acetylcholine↗
PubMed1980

Investigations into the mechanism of morphine and ethanol inhibition in the guinea pig ileum longitudinal muscle strip.

It has been noted that the analgesic property of ethanol bears a marked resemblance to that of morphine. The purpose of this study was to determine if the mechanism of action of morphine and ethanol was similar using the guinea pig ileal longitudinal muscle strip (GPI-LMS). Ethanol (35-260 mM) depressed the twitch response and the acetylcholine- (ACh-), KCl-, and BaCl2-induced contractions to the same extent while having no significant effect on the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic receptors. Morphine (53-530 nM) inhibited the twitch response and to a lesser extent BaCl2- and KCl-induced contractions while having no significant effect on either ACh-induced contractions or the binding of [3H]QNB to muscarinic receptors. Naloxone and increased [Ca2+] reversed the inhibitory effects of morphine but not ethanol. Ethanol appears to inhibit a site after interaction of ACh with the receptor. Mechanism of inhibition of BaCl2 response is also different as naloxone and increased [Ca2+] reverse morphine but not ethanol inhibition Ethanol inhibition in GPI-LMS does not involve the opiate receptor.

Acetylcholine↗
PubMed1980

Respiratory depression produced by diazepam in cats: effect of anaesthesia.

Diazepam (Valium, Roche; 0.37 mg/kg was given by slow injection into the left femoral vein and flushed in with 0.9 % saline. Within 3 min following the i.v. injection of diazepam spontaneous respiration ceased in rats anaesthetized with chloralose; mean arterial pressure fell from a control level of 99.4 (+/- 28.3) mmHg to 32.5 (+/- 13.44) mmHg. If artificial ventilation was initiated immediately upon cessation of respiration, the animal recovered. Cats anesthetized with ketamine (Ketaset, Roger; 44 mg/kg i.m.) showed no respiratory depression following i.v. diazepam injection.

Anesthesia↗
PubMed1979

Pharmacological actions of HS-6, an oxime, on the neuromuscular junction.

The effect of HS-6 [1-(2-hydroxyiminomethylpyridinium)-1-(3-carboxamidopyridinium)-dimethyl ether] on neuromuscular (NM) transmission was investigated using chick biventer cervicis (CBC), rat diaphragm (RD) and guinea pig ileum longitudinal muscle strip (GPLS) preparations. In the CBC preparation HS-6 did not cause a contraction, whereas it produced a dose-related contraction of the GPLS preparation. HS-6 produced a hemicholinium-like NM blockade in the CBC and RD preparations. This was supported by the fact that HS-6 inhibited choline uptake in erythrocytes. HS-6 inhibited the contractions of various nicotinic agonists in the CBC preparation and augmented the acetycholine contractions. The latter was due to AChE inhibition produced by HS-6.

Animals↗
PubMed1979

Echogenic fluid: a pitfall in the ultrasonographic diagnosis of cystic lesions.

Although it is well known that biliary sludge can produce fine diffuse echoes within the gallbladder, it is less commonly appreciated that other cystic structures may contain echogenic fluid and therefore be mistaken sonographically for solid lesions. In this article three cases of splenic cysts and one case each of pyrometrocolpos, hydroureter, and pyonephrosis presented with diffuse fine echoes in the fluid. Three of these cases were misinterpreted as a result of this echogenic appearance. These cases serve to emphasize the need for awareness of the echogenicity of some types of fluid and the value of other signs of cystic lesions besides absence of internal echoes.

Adult↗
PubMed1978

Effect of ethanol, pentobarbital and morphine on the toxicity of hemicholinium-3 and d-tubocurarine in mice.

Pretreatment of mice with either ethanol, pentobarbital or morphine protected against the lethal effects of hemicholinium-3 (HC-3) but not curare. The protective action of these compounds was not due to an induced release of corticosteroids in vivo since administration of prednisolone did not protect against HC-3 toxicity. The protective action of morphine was reversed by Nalline hydrochloride. The results suggest that the site of the protective action of ethanol, pentobarbital and morphine and the site of action of the lethal respiratory depression by HC-3 are central in origin.

Animals↗
PubMed1975

Presynaptic effect of the aziridinium ion of acetylcholine mustard (methyl-2-acetoxyethyl-2'-chloroethylamine) on the phrenic nerve--rat diaphragm preparation.

The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca-2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported date for toxicity of acetylcholine mustard aziridinium ion in the mouse.

Acetylcholine↗