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Biomedical subjects

P K Gessner

Publications and source records attributed to P K Gessner.

At least 19 recordsLinked to original sources
PubMed1987

Freundlich and Langmuir isotherms as models for the adsorption of toxicants on activated charcoal.

The Langmuir isotherm has been widely used to characterize the adsorption of solutes from aqueous solutions. Activated charcoal adsorption data obtained experimentally, using a wide range of adsorbate concentrations, fit the Langmuir isotherm poorly but evidence a good fit to the Freundlich isotherm. Statistical analysis reveals this to be also true of published data that was previously considered to adhere to the Langmuir isotherm. Over the range of possible adsorbate concentrations, the two isotherms predict rather different adsorption behavior. Of the two, the Freundlich isotherm is able to more fully account for observed antidotal effectiveness of activated charcoal in vivo. A method of graphical analysis is advanced that more readily distinguishes the relative goodness-of-fit of the two isotherms. This and the statistical paradigm employed to decide between the two competing hypotheses should allow the adsorption phenomena involving other adsorbents to be re-examined.

Charcoal↗
PubMed1985

Interactions of paraldehyde with ethanol and chloral hydrate.

The interaction of the depressant and toxic actions of paraldehyde with those of ethanol and chloral hydrate were investigated in two strains of male mice by determination of the ED50 for anesthetic action (righting reflex loss) and the 24 hr LD50, respectively. In all instances less than simple additive synergism was observed. Onset and duration times for the anesthetic actions of paraldehyde and ethanol were observed to be almost identical. Investigation of the time of maximum toxic effect revealed paraldehyde itself and mixtures containing 40% or more paraldehyde to be more acutely toxic than ethanol or mixtures containing more than 80% ethanol, suggesting the possibility of different mechanism of toxic action as contributory reasons for the less than simple additivity of the lethal effects of these two agents. The onset and duration of the anesthetic effect of chloral hydrate was longer than that of equipotent doses of paraldehyde, binary mixtures of these two agents having intermediate onset times but much longer duration than either compound, leading to the conclusion the less than simple additivity observed with respect to both the depressant and toxic actions of paraldehyde and chloral hydrate resulted from different time courses of action.

Anesthesia↗
PubMed1984

Pharmacokinetics of paraldehyde disposition in the neonate.

The pharmacokinetic parameters controlling paraldehyde elimination were determined in nine infants infused with paraldehyde at the rate of 150 mg/kg/hr in a 5% solution in 5% dextrose for the treatment of status epilepticus. The mean +/- SEM values for the observed parameters were as follows: rate constant for the disposition of paraldehyde 0.0680 +/- 0.0071 hr,-1 half-life 10.2 +/- 1.0 hr; volume of distribution 1.73 +/- 0.20 L/kg; clearance 0.121 +/- 0.023 L/hr/kg. Phenobarbital administration prior to or within 24 hours of the cessation of paraldehyde infusion decreased both paraldehyde clearance and volume of distribution in a manner linearly related to the logarithm of the phenobarbital dose. The rate constant for paraldehyde elimination was decreased as a linear function of the logarithm of the combined dose of administered phenobarbital and phenytoin. No acetaldehyde was detected in any blood samples. Paraldehyde administration was not correlated with any adverse reactions or toxicities.

Female↗
PubMed1983

Metabolism of paraldehyde to acetaldehyde in liver microsomes. Evidence for the involvement of cytochrome P-450.

A concentration-dependent acetaldehyde (AcH) generation was observed when paraldehyde was incubated with the mouse liver microsomal fraction. The process, which exhibited a requirement for oxygen and NADPH and was inhibited by carbon monoxide, was found to have a Km of 17.9 mM with respect to paraldehyde and a Vmax of 40.1 nmoles/mg protein/min with respect to AcH formation. NADH was much less effective as an electron donor than NADPH, though a more than additive increase in AcH generation was observed when both of these nucleotides were added to the incubation. The rate of microsomal AcH generation from paraldehyde was increased 2.5-fold by pretreatment of the mice with phenobarbital but only 0.6-fold by pretreatment with 3-methylcholanthrene. Pretreatment with 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A) resulted in 54% inhibition of the reaction rate. Addition of metopirone to the incubation inhibited AcH generation in a concentration-related fashion, the inhibition being greatest, proportionately, in microsomes from phenobarbital-pretreated animals. The above results conclusively indicate the involvement of cytochrome P-540 mixed function oxidase in the formation of AcH from paraldehyde by mouse liver microsomes. It is also postulated that this process may be accomplished in the reaction analogous to O-dealkylation.

Acetaldehyde↗
PubMed1983

Metabolism of [14C]paraldehyde in mice in vivo, generation and trapping of acetaldehyde.

The metabolic fate and the kinetics of paraldehyde metabolism after the i.p. administration of a 400 mg/kg dose of this agent were investigated in mice. Paraldehyde was found to have a biologic half-life in this species of 41.5 min, its disappearance from blood being governed by a single component exponential process with a rate constant of 0.0167 min-1. By using [14C]paraldehyde, it was found that the major process responsible for paraldehyde disappearance was its metabolic degradation to carbon dioxide, a two-step process; the first step of which was inhibited by pretreatment with SKF-525A. The rate constants for the two steps being 0.0121 and 0.0212 min-1, respectively; on the basis of these rate constants it was calculated this pathway would account for 72.3% of the administered dose at infinite time. A second major pathway for the disposition of paraldehyde was its excretion in expired air, which, at infinite time, would account for 9.6% of the dose. No acetaldehyde (AcH) could be detected in either the breath or the blood of mice after paraldehyde administration. Pretreatment with the aldehyde dehydrogenase inhibitors, pargyline or cyanamide, did not result in the accumulation or excretion of detectable amounts of AcH. Pretreatment of mice administered [14C]paraldehyde with both cyanamide and D-penicillamine,, an AcH sequestering agent, resulted, however, in urinary excretion of the 14C-labeled condensate of D-penicillamine and AcH showing AcH to be formed from paraldehyde. The above results indicate that paraldehyde is rapidly metabolized in vivo to carbon dioxide and that AcH is an intermediary product in this process.

Acetaldehyde↗
PubMed1981

Sociomedical issues in the curriculum: a model for institutional change.

An institutional strategy has been developed that permits consideration of sociomedical issues in some depths throughout the undergraduate curriculum. A major component of the strategy is the appointment by the dean of multidisciplinary education committees, each concerned with one sociomedical problem area. Eight such committees have been appointed, and each has developed a small group seminar course in its area. In the freshman year, each student is required to choose one of these seminars, or "selectives," and to participate in it for two semesters. Analysis of grades in the required basic science courses has demonstrated that participation in the selectives has no adverse effect on student performance in the other courses. These and other activities of the education committees have brought about changes elsewhere in the educational program.

Achievement↗
PubMed1979

Effects of meperidine on operant behavioral thermoregulation in mice under conditions of symmetrical thermal drive.

The effects of meperidine on operant behavioral thermoregulation were investigated using a convective thermal controller and mice trained to alternate at will the thermal-drive condition, changing it from an air flow of 15 degrees C to one of 45 degrees C, and vice versa. Administration of 15 mg/kg meperidine resulted in significantly lower response rates, a significantly larger fraction of time spent in one (mostly cold) drive condition, and significantly lower body temperatures than administration of saline. In a second experiment the animal was automatically returned to the hot-drive condition every 3 min unless it had been exposed to this condition in the previous 0.4 min although otherwise it remained free to alternative drive conditions at will. Under these conditions, meperidine-treated animals also spent significantly more time in cold drive and had significantly lower body temperatures than control animals, in spite of lower response rates. Pretreatment with 4.5 mg/kg tranylcypromine (4 h prior) did not significantly alter the effects of meperidine administration in either experiment.

Animals↗
PubMed1979

Serotonin receptor binding affinities of tryptamine analogues.

Using a rat fundus model, the serotonin (5-HT) receptor binding affinities of 27 tryptamine analogues were determined. Factors which might affect affinity were examined, e.g., lipids solubility, as reflected by partition coefficient, and pKa. Structure-activity relationships were developed and are discussed in terms of substituents on the terminal amine, the side chain, and the indole 1 position, the 5 position, and at other positions on the indolic nucleus. If lipid solubility and metabolism can be accounted for, there appears to be a parallelism between 5-HT receptor binding affinities and the hallucinogenic (psychotomimetic) potencies of several of these compounds.

Animals↗
PubMed1979

Bufotenine esters.

Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl esters of bufotenine were prepared for future pharmacological evaluation. Unexpectedly, it was found that these esters all possess a relatively high affinity for the serotonin receptors of the isolated rat stomach fundus preparation. A semiquantitative chromatographic measurement of ester hydrolysis suggests that extensive hydrolysis of the esters to bufotenine does not occur under the conditions of the affinity assay.

Animals↗
PubMed1977

The electronic and serotonin receptor binding affinity properties of N,N-dimethyltryptamine analogs.

The electronic properties of a series of N,N-dimethyltryptamines and related analogs, for which binding affinity data are available, were examined using both a pi-electron and an all-valence electron method. The results suggest that affinity is related to the ability of these compounds to donate electrons in a localized charge transfer manner from the 4-position of the indole nucleus.

Chemical Phenomena↗