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Biomedical subjects

E F Domino

Publications and source records attributed to E F Domino.

At least 19 recordsLinked to original sources
PubMed1995

Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Zinc protoporphyrin (ZnPP) has multiple actions. It is an interleukin-1 antagonist as well as a hemeoxygenase inhibitor. Interleukin-1 is produced in ischemic brain and probably contributes to ischemic injury, although the role of heme oxygenase during ischemia is unknown. Whether ZnPP treatment is more effective before or after ischemia, as well as whether it is more protective in permanent or temporary cerebral ischemia, is also unknown. Therefore, we investigated the effect of ZnPP on infarction size and edema in a rodent model of temporary and permanent focal cerebral ischemia. METHODS: Two groups of adult male Sprague-Dawley rats were pretreated with either 50 mg/kg ZnPP IP or saline and subjected to permanent middle cerebral artery occlusion 30 minutes later. Four additional groups of animals were subjected to 2 hours of temporary middle cerebral artery occlusion followed by 22 hours of reperfusion. Two of these groups were pretreated 30 minutes before middle cerebral artery occlusion with either 50 mg/kg ZnPP IP or saline. The other groups received ZnPP at either 2 or 4 hours after middle cerebral artery occlusion. Regional cerebral blood flow in the ischemic cortex was monitored with laser Doppler flowmetry. Cerebral infarct size and brain water were measured 24 hours after the onset of either form of ischemia. RESULTS: Regional cerebral blood flow after occlusion was approximately 13% to 20% of baseline after either permanent or temporary ischemia. ZnPP had no effect on regional cerebral blood flow, infarct size, or edema formation in permanent ischemia. In contrast, pretreatment significantly reduced infarct size (17.2 +/- 6.6% in controls versus 6.2 +/- 2.9% in pretreated rats) and edema formation (center zone, 4.00 +/- 0.71% water in controls versus 1.18 +/- 0.26% water in pretreated rats) in the model of temporary ischemia, but treatment after occlusion had no effect. CONCLUSIONS: ZnPP treatment protected the brain when administered early in the temporary ischemia model.

Animals↗
PubMed1992

Effects of tobacco smoking on the topographic EEG II.

1. Tobacco smokers are well aware of the long term hazards of tobacco smoking, yet they continue to smoke. Presumably people smoke because of short term gains due to nicotine. 2. The mechanism by which nicotine is a drug reinforcer still needs a great deal of study. The specific aim of the present study was to determine the effects of tobacco smoking on the topographic EEG of 12 hr deprived heavy tobacco smokers. 3. Seven normal adult tobacco smokers of mixed sex were recruited into the study and compared with six normal nonsmokers of similar age and sex. 4. A Grass Model 8-24D EEG and 16 different scalp monopolar electrodes were used to record the EEG using both ears as reference before and after smoking. EKG lead II was recorded on channel 17. Blood pressure was measured by auscultation. Exhaled CO was measured using a CO detector. Computer analysis of the EEG data was run of line on a Zenith 386/25 microcomputer using RHYTHM 7.1. The same system was used to store the EEG in digitized form. The maximum number of 4 sec artifact free epochs in a 3 min recording period with eyes open and then closed was used before and after low and high nicotine tobacco or sham smoking. 5. The hypothesis of this research was confirmed, i.e., that tobacco smoking of high nicotine cigarettes (about 2.0 mg/cigarette) would cause a shift in EEG alpha rhythm to higher frequencies in more diffuse midline cortical structures. In other studies an increase in alpha rhythm has been correlated with an awake relaxed behavioral state. 6. A heart rate increase was a more sensitive index of tobacco smoking than an increase in arterial blood pressure. Exhaled smoking CO levels correlated with the nicotine and tar content of the cigarette.

Adult↗
PubMed1989

Further observations on the effects of subhypnotic doses of midazolam in normal volunteers.

Our studies on the effects of subhypnotic doses of midazolam in healthy adult volunteers have been extended with special emphasis on clinical electrophysiological endpoints of sedation and attention coupled with various tests of memory. We measured the many components of the P300 event-related brain potential to infrequent (rare) tones. Midazolam HCl was given in a dose of .02 mg/kg i.v. three times at approximately 15-minute intervals after obtaining baseline electrophysiological recordings and memory test results. Marked individual variation was observed with these small doses of midazolam. Some subjects were markedly sedated, whereas others showed relatively little sedation. Electroencephalogram (EEG) beta activity increased while alpha activity decreased following midazolam. Even though the subjects given midazolam were awake, there was a striking attention deficit that correlated well with the accuracy of counting rare tones and the alterations in various components of the late auditory event-related brain potential.

Adult↗
PubMed1988

Effects of selected muscarinic cholinergic antagonists on [3H]acetylcholine release from rat hippocampal slices.

A number of cholinergic muscarinic (M) agonists and antagonists were studied for their ability to enhance tritiated acetylcholine ([3H]ACh) release from electrically field-stimulated rat hippocampal slices. A Ca++-free medium and carbachol, but not nicotine, inhibited [3H]ACh release. Atropine, methylatropine and dexetimide produced concentration-dependent increases in [3H]ACh release to a maximum of about 50% above control. Aprophen and benactyzine produced a maximal response 25 to 35% above control. The selective M1 antagonist pirenzepine had the least effect on [3H]ACh release. Of the nonspecific M1-M2 antagonists studied, benactyzine produced the least amount of [3H]ACh release. The order of potency of the M antagonists in promoting a 15% increase in [3H]ACh release was aprophen greater than benactyzine greater than methylatropine greater than dexetimide greater than pirenzepine greater than atropine. However, the order of promoting maximal release of [3H]ACh was atropine greater than dexetimide greater than methylatropine greater than aprophen greater than benactyzine greater than pirenzepine.

Acetylcholine↗
PubMed1988

Instrument flight performance under the influence of certain combinations of antiemetic drugs.

Two different combinations of antiemetic drugs were evaluated using a digital flight simulator. Drug treatments consisted of a lactose placebo, a combination of thiethylperazine (10 mg) and cimetidine (300 mg), and a combination which added promethazine (25 mg) to the two-drug combination. The performance effects of these combinations were evaluated on both a dual task (instrument flight task with the Sternberg Memory Scanning task) and a single task condition (Sternberg task only) for 3 h post drug ingestion. Analysis indicated a significant treatment effect on three of the six flight performance variables and that the three-drug combination, containing promethazine, was primarily responsible for the decrease in performance. Implications for operation in a radiation environment are that thiethylperazine and cimetidine will not cause significant performance decrements, but the addition of promethazine to those two drugs will significantly impair performance. The Sternberg task was sensitive to changes in workload.

Adult↗
PubMed1987

Extracellular calcium alters frequency modulation of [3H]acetylcholine release from rat hippocampal slices.

The concentration of extracellular Ca2+ has been shown to enhance or attenuate [3H]acetylcholine (ACh) release subsequent to a conditioning stimulus in rat brain hippocampal slices. Slices were incubated in vitro in [3H]choline solution. Subsequently the slices were subjected to two consecutive electrical stimulations separated by 15 or 30 min at 0.25, 1, 4 and 16 Hz and [3H]ACh release was assessed. It was found that a conditioning stimulus may reduce [3H]ACh release during a second stimulation. This phenomenon is frequency related and disappears when the two stimulations are 30 min apart. High extracellular Ca2+ (4.0 mM) further attenuated [3H]ACh release during the second stimulation, whereas low Ca2+ (0.32 mM) abolished the decrease in [3H]ACh release following the second stimulation in all frequencies tested.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Metaphit, a proposed phencyclidine receptor acylator: disruption of mouse motor behavior and absence of PCP antagonist activity.

Metaphit, a derivative of phencyclidine (PCP) differing by the meta substitution of an isothiocyanate group on the phenyl ring, was given into the lateral cerebral ventricle of mice alone and as a pretreatment to the subsequent i.p. injection of PCP and pentobarbital. Drug effects on motor performance as an index of neurologic impairment were quantified using the mouse platform test. The ED50 of metaphit to disrupt mouse platform behavior 5 min after i.c.v. administration was 0.48 mumol. An isobolographic analysis indicated that metaphit interacted additively with PCP and pentobarbital. Animals that recovered 24 or 48 hr after a large dose (1 mumol i.c.v.) of metaphit or phenylisothiocyanate, a nonspecific acylating control substance, were then given PCP (18.3 mumol/kg i.p.) or pentobarbital (76.7 mumol/kg i.p.). Both agents enhanced PCP-induced failure of mice to climb to the top of the platform. Metaphit also enhanced pentobarbital-induced failure of mice to climb to the top of the platform. No evidence was obtained that metaphit antagonized the behavioral effects of PCP in mice.

Animals↗
PubMed1987

Relation of plasma morphine concentrations to severity of abrupt withdrawal in morphine-dependent monkeys.

Plasma morphine levels were measured during abrupt withdrawal in four chronically dependent female monkeys. Approximately 12 hr after withdrawal, the morphine plasma concentrations were about 8 to 10 ng/ml, at which time all of the animals showed mild to moderate symptoms of opiate withdrawal. Severity of withdrawal showed a negative correlation (r = -0.93, P less than .001) with the falling phase of plasma morphine. It may be concluded that, under the conditions of this experiment, significant morphine withdrawal symptoms arose despite measurable plasma concentrations of morphine and that the relationship between plasma concentrations and withdrawal may be quantified according to a linear pharmacokinetic model for a given chronic dose (3.0 mg/kg q 6 hr) of morphine.

Animals↗
PubMed1986

Opioid-hallucinogen interactions.

Before the advent of neuroleptics, opioids such as morphine were used occasionally in the treatment of schizophrenia and other mental disorders. Recent interest in the possible therapeutic role of endogenous opioid peptides in various mental states has prompted a new look at the opioids. The present paper summarizes the research to date in the author's laboratory on opioid-hallucinogen interactions. A model behavioral state was induced in rats with N,N-dimethyltryptamine (DMT) or lysergic acid diethylamide-25 (LSD). Several mu opioid agonists, antagonists, and synthetic enkephalin analogs interacted with DMT and LSD. Adult male Holtzman rats trained on a positive reinforcement fixed ratio four (FR4) behavioral schedule (i.e., a reward of 0.01 ml sugar-sweetened milk was earned on every fourth bar press) were used in these studies. DMT (3.2 and 10.0 mg/kg) given with a 0.9% NaCl pretreatment IP, disrupted established food rewarded FR4 bar pressing behavior in a dose related fashion. Pre-determined behaviorally ineffective doses of mu opioid agonists showed selective biphasic effects against DMT and LSD. Low doses antagonized the effects of both hallucinogens, whereas larger doses enhanced their effects. In contrast to the antagonistic effects of low doses of mu opioid agonists, the mu-kappa opioid antagonist (-)-naloxone enhanced the effects of DMT and LS. (-)-Naloxone enhanced the effects of DMT and LSD. Potentiation of DMT-induced behavioral disruption was attributed to a stereospecific opioid antagonist effect of (-)-naloxone in that the (+)-naloxone enantiomer failed to potentiate the effects of DMT. Further studies are indicated to determine hallucinogen-opioid interactions in various species, including man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Three forms of xanthine: acceptor oxidoreductase in rat heart.

The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.

Animals↗
PubMed1986

Pharmacologic evidence that high dose chronic amitriptyline and desipramine down-regulate alpha 2-receptor-mediated hypothermia in the rat.

The effects of a three week course of treatment of amitriptyline (AMI) and desipramine (DMI) (3.2 and 10 mg/kg, s.c., b.i.d.) were studied on the hypothermic response to clonidine (0.1 mg/kg, s.c.) in male adult albino rats. Single doses of clonidine in normal unmedicated rats produced a marked (about 2 degrees C) fall in body temperature. In contrast, 0.9% NaCl control injections had no significant effect. The clonidine-induced hypothermia was prevented by yohimbine pretreatment (3.2 mg/kg, i.p., 1/2 hr before), suggesting an alpha 2-mediated response. On days 8 and 14 of chronic tricyclic antidepressant (TCA) treatment, the hypothermic response was prolonged. Four days after the abrupt withdrawal of 20 days of TCA treatment (10 mg/kg, s.c., b.i.d.), the clonidine-induced hypothermia response was attenuated consistent with down-regulation of alpha 2-receptors. This latter effect was not observed with a dose of 3.2 mg/kg, s.c., b.i.d. of either TCA.

Amitriptyline↗
PubMed1986

Comparative antitussive effects of dextrorphan, dextromethorphan and phencyclidine.

The possible antitussive effects of dextrorphan (the (+) isomer of levorphanol) and phencyclidine (PCP) were compared to well known antitussive properties of dextromethorphan in the post-halothane anesthetized decerebrate cat in which cough was elicited by direct electrical stimulation of the cough center. Dextrorphan, when injected i.a. (0.05-0.32 mg kg-1) or i.v. (1 to 3 mg kg-1), PCP i.a. (0.1-0.32 mg kg-1) or i.v. (1.0 mg kg-1) had no effect on electrically elicited cough. After i.v. administration, dextrorphan caused a variable effect on respiration but did not have any respiratory effect with i.a. administration of the drug. PCP injection i.a. at 0.32 mg kg-1 severely inhibited respiration though coughing could still be elicited. But i.v. administration of 1.0 mg/kg-1 suppressed both cough and respiration for several hours. Dextromethorphan inhibited cough upon both i.a. and i.v. injection. The mean effective i.a. dose was 0.063 mg kg-1. A ten times higher dose was necessary (0.65 mg kg-1) for cough suppression by the i.v. route. It is concluded from the i.a./i.v. ratio that dextromethorphan has specific central antitussive activity not possessed by dextrorphan and PCP.

Animals↗