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Biomedical subjects

W M Davis

Publications and source records attributed to W M Davis.

At least 73 records · Page 4Linked to original sources
PubMed1980

Synergism of the toxicity of physostigmine and neostigmine by lithium or by a reserpine-like agent (Ro4-1284).

A single sublethal i.p. dose of lithium chloride (300 mg/kg or 7.1 meq/kg) followed 12 h later by an otherwise sublethal s.c. dose of physostigmine sulfate (1.0 mg/kg) resulted in 90% mortality among male rats following a pronounced cholinergic syndrome, including convulsions. This confirms a previous report of a lethal synergism of physostigmine after subacute dosing with lithium. Mortality could be completely prevented by 1.0 mg/kg of atropine sulfate given 30 min before physostigmine, but was incompletely, if at all, reduced by selective peripheral cholinergic blockers, methylatropine bromide (0.5, 1.5 mg/kg) or glycopyrrolate (1 mg/kg). This suggested a predominantly central site for the toxic interaction. However, a similar synergism of lethality caused by neostigmine methylsulfate (0.3 mg/kg, s.c.) after treatment with lithium, which could be eliminated by methylatropine or glycopyrrolate, indicates that lithium may also produce lethal synergism of a cholinesterase (ChE) inhibitor that does not act centrally. Ro4-1284, an agent that has reserpine-like actions, was tested in combination with physostigmine or neostigmine; it showed synergism of toxicity nearly the same as in the case of lithium plus the cholinergic agents. These findings support the hypothesis that lithium causes the toxic synergism via a reduction of adrenergic activity, leading to an imbalance between adrenergic and cholinergic influences and a consequent failure to tolerate the effects of the ChE inhibitors. A potential hazard for the clinical use of physostigmine and neostigmine, concurrently with lithium or reserpine-like agents, it suggested.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1980

Fluorometric determination of adenosine nucleotide derivatives as measures of the microfouling, detrital, and sedimentary microbial biomass and physiological status.

Adenosine, adenine, cyclic adenosine monophosphate (AMP), AMP, nicotinamide adenine dinucleotide, adenosine diphosphate, and adenosine triphosphate (ATP) were recovered quantitatively from aqueous portions of lipid extracts of microfouling, detrital, and sedimentary microbial communities. These could be detected quantitatively in the picomolar range by forming their 1-N-etheno derivatives and analyzing by high-pressure liquid chromatography with fluorescence detection. Lipid extraction and subsequent analysis allowed the simultaneous measurement of the microbial community structure, total microbial biomass with the quantitative recovery of the adenine-containing cellular components, which were protected from enzymatic destruction. This extraction and fluorescent derivatization method showed equivalency with the luciferin-luciferase method for bacterial ATP measurements. Quick-freezing samples in the field with dry ice-acetone preserved the ATP and energy charge (a ratio of adenosine nucleotides) for analysis at remote laboratories. The metabolic lability of ATP in estuarine detrital and microfouling communities, as well as bacterial monocultures of constant biomass, showed ATP to be a precarious measure of biomass under some conditions. Combinations of adenosine and adenine nucleotides gave better correlations with microbial biomass measured as extractable lipid phosphate in the detrital and microfouling microbial communities than did ATP alone. Stresses such as anoxia or filtration are reflected in the rapid accumulation of intracellular adenosine and the excretion of adenosine and AMP into the surrounding milieu. Increases in AMP and adenosine may prove to be more sensitive indicators of metabolic status than the energy charge.

Journal Article↗
PubMed1979

Extravasation cyst diagnostic curettement: a treatment. Report of 15 cases and suggested treatment.

Fifteen cases of extravasation lesions of the mandible have been treated. In six cases, the lesions were entered surgically, explored, and directly curetted following preliminary diagnosis by needle aspiration. Healing was uneventful in all cases, and bone regeneration occurred rapidly. Hemorrhage was easily controlled, and the surgery was considered a minor procedure. Nine cases were treated by a combined diagnostic-curettement technique. The entire procedure was quickly performed under local anesthesia. There was little chance of injury to surrounding structures, and there were few postoperative sequelae. The resolution of the lesion and bone regeneration occurred in a time span similar to that of the surgical treatment of lesions.

Adolescent↗
PubMed1979

Reinforcement with intragastric infusions of ethanol: blocking effect of FLA 57.

Suppression of oral intake of ethanol by FLA 57 has been reported for rats and was attributed to an inhibition of dopamine beta-hydroxylase. We have demonstrated the ability of FLA 57 (50 mg/kg, IP) to suppress bar-pressing for intragastric (IG) delivery of doses of ethanol (25 mg/kg). This indicates that the effect on oral intake of ethanol may not be attributed to a taste factor, e.g., a decreased palatability of the ethanol solution. The same dose of FLA 57 did not suppress responding for IG doses of sweet milk. Thus, there was not an impairment of appetitive behavior in general through some nonspecific depressant or toxic action. Furthermore, the primary reinforcing action of ethanol, when used to establish a buzzer as a conditioned reinforcer through repeated pairings, was blocked if FLA 57 was given before pairings. This was evidenced by a failure of such rats to bar-press above the baseline level in a later test of conditioned reinforcement, which contrasted with the increased responding seen for rats receiving saline instead of FLA 57 before ethanol. These data support the previous findings on oral ethanol and confirm that FLA 57 can impair the mechanism by which ethanol produces positive reinforcement in rats.

Animals↗
PubMed1979

Toxic interaction between narcotic analgesics and inhibitors of catechol-O-methyltransferase.

A lethal synergism between morphine and tropolone, an inhibitor of catechol-O-methyltransferase, was previously noted in adult male Holtzman rats. The present research demonstrates that this phenomenon generalizes across factors of sex, age, strain (Sprague--Dawley, Wistar) and species (Swiss albino mice). Acute toxicity was also significantly increased (1.5--1.9 times) in the case of codeine, methadone, meperidine and levorphanol, but to a lesser extent than for morphine (4.0 times) in the S-D strain. Another COMT inhibitor, 3,5-dihydroxy-4-methoxybenzoic acid, interacted with morphine in S-D rats to an equal degree as did tropolone. Post-treatment with 1 mg/kg of naloxone in rats or naltrexone in mice reduced the high lethality associated with morphine plus tropolone. There was a pronounced lowering of whole brain norepinephrine (NE) level after morphine plus tropolone in Wistar rats with doses of each component that alone caused no change in NE. Brain dopamine (DA) was elevated by tropolone and by its combination with morphine. Each drug alone caused slight lowering of brain serotonin. Enhancement by tropolone of the toxicity of (+)-amphetamine in mice and rats was of similar magnitude as for morphine. The possible role of brain NE and/or DA in the sensitivity to acute toxic effects of opioids in rodents is suggested by these data, as well as a parallel in this regard with amphetamine-type stimulants.

Aging↗
PubMed1979

Lethal synergism between morphine or other narcotic analgesics and propranolol.

Interactions of (+/-)-propranolol HCl with various narcotics were determined in albino rats. The 24-h intraperitoneal (i.p.) LD50 of morphine sulfate + saline was 15--16 times greater than for morphine + propranolol in both sexes although morphine was nearly twice as toxic to males as to females. The potency ratios for LD50's with saline vs. with propranolol were: codeine, 1.9, (+/-)-methadone, 6.0; (-)-alpha-acetylmethadol, 2.8 (72 h). The toxicity of levorphanol also was greatly increased with propranolol, but the dose-effect relationship showed non-parallelism vs. levorphanol + saline. Albino mice and mongrel dogs also showed synergism between morphine and propranolol. Mortality after morphine and propranolol was antagonized by naloxone or naltrexone in rats and mice. The potency ratio in rats for morphine + saline vs. morphine + practolol was 3.5. However, the synergism between propranolol and the narcotics probably was unrelated to beta-adrenergic blocking effects of propranolol because of the apparent equivalence of (+)-, (-)- and (+/-)-propranolol in rats for synergism with morphine.

Analgesics, Opioid↗
PubMed1979

Experimental diazepam intoxication in rodents: physostigmine and naloxone as potential antagonists.

The ability of physostigmine and naloxone to reverse the loss of righting reflex (LRR) induced by diazepam was tested in mice and rats. Physostigmine was ineffective under our test conditions, but high doses of naloxone reduced the duration of LRR in both species. However, the LD50 of diazepam in mice was unaltered by 100 or 150 mg/kg of naloxone given 1 hr after LRR to model an antidotal situation. Use of a longer duration narcotic antagonist, naltrexone (172 mg/kg), in the same design likewise failed to elevate the LD50 for diazepam. These data give limited support to prior suggestions for clinical usefulness of naloxone, although not for physostigmine, in the management of intoxication caused by diazepam.

Animals↗
PubMed1979

Morphine lethality in rats: effects of various central receptor blocking agents.

A previous report of a lethal potentiation between sublethal doses of morphine and the beta-adrenergic blocker propranolol was confirmed for Sprague-Dawley rats. An alpha-adrenergic blocker, phentolamine, also showed a lesser but significant potentiation, as did a moderate dose of atropine. No synergism was noted between morphine and methylatropine, haloperidol or methysergide. Phentolamine and a lower dose of atropine, which did not synergize with morphine, both added significantly to the lethality of the combination of morphine and propranolol, whereas methylatropine, haloperidol and methysergide had no significant effect to synergize or antagonize mortality.

Adrenergic alpha-Antagonists↗
PubMed1978

Noradrenergic role in the self-administration of ethanol.

Involvement of noradrenergic and/or dopaminergic processes of the brain in self-administration behavior toward ethanol was assessed in rats allowed to lever-press for 25 mg/kg intragastric doses on a CRF schedule. Initial access to infusions of saline for establishing an operant baseline was followed by one 10-hr session on acquisition contingencies for ethanol and then one extinction session on saline. Prior to a reacquisition session, rats were treated with either (a) saline, (b) alpha-methyl-p-tyrosine (AMT; 225 mg/kg), (c) 1-phenyl-3-(2-thiazolyl)-2-thiourea (U-14,624; 600 mg/kg or 300 mg/kg), or (d) haloperidol (3.5 mg/kg). Only the saline-pretreated control group and the haloperidol-treated rats reacquired lever-press behavior. Groups treated in like fashion, but pressing for a sweet milk reinforcer, all showed reacquisition. Thus, the effects of AMT and U-14,624 are attributed to an inteference with the reinforcing effect of ethanol infusions. Brain levels of norepinephrine were depleted by both compounds, dopamine was depleted only by AMT, and serotonin was elevated by 600 mg/kg of U-14,624 but unaffected by 300 mg/kg. These results suggest that a cerebral noradrenergic system plays an important role in the reinforcing effect of ethanol without an involvement of dopaminergic systems.

Animals↗
PubMed1978

Effect of 1-alpha-acetylmethadol (LAAM) on various physiological parameters in the conscious dog.

LAAM was administered intravenously to conscious dogs at doses of either 0.1, 0.3 or 1.0 mg/kg. Cardiopulmonary responses were measured prior to drug administration, 0.5 hr post-drug and hourly thereafter. All doses produced a sleep-like state which was dose-related in duration (3-14 hr). Cardiac output, heart rate, respiratory rate and minute volume were decreased below mean pre-drug control values after drug administration in the two higher dosage groups; cardiac output in both groups failed to return to pre-drug control levels. Additionally, total peripheral resistance was elevated in these dosage groups although mean arterial pressure remained stable. Arterial pCO2 increased and arterial pH decreased as respiratory rate and minute volume decreased. Depression of rectal temperature occurred only in response to the highest dose.

Animals↗
PubMed1978

Interactions of catecholaminergic receptor blockers with lethal doses of amphetamine or substituted amphetamines in mice.

Lethality to both isolated and aggregated mice was determined for graded i.p. doses of d-amphetamine, dl-4-methoxyamphetamine (PMA), dl-2,5-dimethoxyamphetamine (DMA), dl-2,5-dimethoxy-4-bromoamphetamine (DOB), dl-2,5-dimethoxy-4-methylamphetamine (DOM) and d1-3,4-methylenedioxyamphetamine (MDA). Haloperidol (2.0 mg/kg), propranolol (10 mg/kg) and phenoxybenzamine (30 mg/kg) were tested for ability to antagonize the lethal effects of amphetamine and its derivatives. Considerable protection against amphetamine lethality was produced by haloperidol in both isolated and aggregated mice and by phenoxybenzamine in isolated mice, but propranolol was ineffective. An equivalent degree of protection was not achieved by use of any of the three agents before PMA, DMA or DOB. Protection against DOM was achieved only with phenoxybenzamine and only for isolated mice. Extensive protection against MDA was supplied by both phenoxybenzamine and propranolol for either condition of housing. Despite close structural relationships between the toxicants, the antidotal effectiveness of the receptor-blocking agents seemed quite limited and specific, and did not support any generalizations.

Amphetamines↗