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Biomedical subjects

J H Bidanset

Publications and source records attributed to J H Bidanset.

At least 19 recordsLinked to original sources

Amygdala kindling in immature rats: proconvulsant effect of the organophosphate insecticide-chlorpyrifos.

Administration of the organophosphate insecticide, chlorpyrifos to immature rats exerted a proconvulsant effect on seizures induced by kindling. Chlorpyrifos was administered to 16 or 17 day old rats in a dose range of 0.3 to 10 mg/kg, subcutaneously. Amygdala kindling was performed by stimulating the rats every 15 minutes to a total of 20 stimulations. Kindling occurred more rapidly in the chlorpyrifos treated rats than vehicle treated rats, the proconvulsant effect was dose-dependent. The proconvulsant effect of chlorpyrifos was more pronounced in the early stages of kindling, indicating a possible increase in local excitability of the amygdala in the presence of chlorpyrifos. Chlorpyrifos also reduced the after discharge threshold in the amygdala in a dose-dependent manner and increased the duration of after discharges elicited by electrical stimulus, indicating an increase in excitability of the amygdala. The effects of chlorpyrifos on kindling were additive with xylene: the proconvulsant effect in the early stages of kindling was greatly enhanced by xylene. Xylene, administered alone as a 0.2% solution, reduced the after discharge threshold of the amygdala, increased the after discharge duration and increased the rate of kindling. These experiments demonstrate a proconvulsant effect of chlorpyrifos in amygdala kindling and this proconvulsant action is additive with xylene.

Amygdala↗

Embryotoxicity and neurotoxicity in rats associated with prenatal exposure to DURSBAN.

DURSBAN (DB; active ingredient chlorpyrifos) is a widely-used organophosphate insecticide. The teratogenic and neurotoxic potential of DB was evaluated in rats in utero by exposing embryos on days 0-7 or days 7-21 of development. These prenatal exposures to DB (0.03, 0.1 or 0.3 mg chlorpyrifos/kg, ip) induced physical abnormalities and embryotoxicity. Rat pups which had been exposed to 0.3 mg chlorpyrifos/kg prenatally demonstrated significant behavioral neurotoxicity on postnatal day 16 in the rotorod test compared to time-matched saline-infused litters. Exposure to DB on postnatal day 3, 10 or 12 also caused neurotoxicity as evaluated by the rotorod test. Our studies suggest prenatal exposure to relatively low concentrations of DB may be associated with embryotoxicity, fetal lethality and behavioral neurotoxicity.

Animals↗

The distribution of ethanol in postmortem blood specimens.

Ethanol was determined by gas chromatography in a variety of tissues and body fluids secured at autopsy in 61 cases. The specimens tested included right and left heart blood, femoral blood, pericardial fluid, cerebrospinal fluid, vitreous humor, urine, stomach contents, and brain. Statistical analysis of the cases revealed no significant differences among the various blood sites tested. However, the variations in blood ethanol concentrations among the various sampling sites within each case were as follows: 40 cases showed differences of less than 25%; 16 cases revealed variability between 25% and 50%, 4 cases had differences exceeding 50%. In one case, satisfactory blood analyses could not be accomplished. The larger variances occurred especially in those instances in which stomach alcohol concentration was 0.50% or greater. In one case, the variability amongst the different blood sites exceeded 400% (femoral blood--0.043%, right atrium--0.070%, root of aorta--0.156%); the brain was 0.050%, and the stomach contents was 1.2%. For all 61 cases, variances in blood alcohol content among the different sampling sites in a single cadaver ranged from 1.8 to 428%.

Absorption↗

Percutaneous in vivo and in vitro absorption of lead.

Diffusion tubes were used to measure the degree of in vitro penetration of tetrabutyl lead, lead naphthanate, lead nuolate, lead acetate and lead oxide in excised guinea pig skin and human skin from autopsy. Tetrabutyl lead demonstrated the greatest penetration in skin from both guinea pig and man. Lead nuolate, lead naphthanate and lead acetate followed in descending order in the human tissue. A similar pattern occurred with guinea pig skin in most cases. There were no measurable amounts of lead oxide absorbed in either species. In vivo absorption was measured by applying 300 mg/kg tetrabutyl lead, lead nuolate, lead naphthanate or lead oxide to the shaved backs of guinea pigs for 7 d under occluded wrappings. Tetrabutyl lead was present in tissues in the highest quantities. Lead nuolate was present in greater amounts than lead naphthanate in the liver and kidneys. Lead acetate was the most poorly absorbed with the exception of lead oxide which demonstrated no absorption.

Animals↗

A review of carboxymyoglobin formation: a major mechanism of carbon monoxide toxicity.

Clinical data suggest, and experimental studies indicate direct cardiotoxic effects of carbon monoxide, apart from carboxyhemoglobin formation. Carbon monoxide interactions with cytochrome oxidase and myoglobin are suspect. Of these, myoglobin is the favored tissue target for carbon monoxide binding. On what evidence? Examination of the literature reveals the following: A 16% greater "volume of distribution" (Vd) for carbon monoxide, versus other blood volume indicators, concentrating in skeletal and cardiac muscle; A high myoglobin content in these tissues corresponding to this "excess" Vd for carbon monoxide; Evidence from animals of significant carboxymyoglobin concentrations; Hemeprotein independent changes produced by carbon monoxide which promote carbon monoxide-myoglobin interactions; A high ratio of deoxymyoglobin (carbon monoxide binding form) to oxymyoglobin intracellularly; Direct intercellular measurements of oxymyoglobin saturations and "cycling" in vivo illustrating favorable conditions for carbon monoxide binding; Data indicating decrements in cardiac performance with loss of functional myoglobin; Evidence that myoglobin is important to the proper functioning of cardio-adaptive mechanisms in stress. The total picture of carbon monoxide poisoning must take into account pathogenic effects due to carboxymyoglobin formation.

Carbon Monoxide↗

Cytotoxic changes induced in rat-liver cells by short-term exposure to acetylethyltetramethyltetralin.

The livers of Sprague-Dawley female rats examined by electron microscopy after oral administration of one, two or three doses of acetylethyltetramethyltetralin (AETT) demonstrated that this compound is a hepatotoxin which induces classic degenerative changes as well as effects on the nucleolus. This suggests that AETT not only affects cytoplasmic homeostasis but may also have an effect upon protein synthesis.

Administration, Oral↗

Comparison of bioassay, high-performance liquid chromatography, and fluorescence polarization immunoassay for quantitative determination of vancomycin in serum.

This investigation was designed to compare three assay techniques, the traditional bioassay (agar diffusion), and two more recent techniques, high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA), for the determination of vancomycin concentrations in serum. One hundred clinical samples obtained from patients receiving vancomycin were assayed by each method. The results from each assay were compared using linear regression analysis. The resultant correlation coefficients were as follows: 0.9996 for the HPLC versus FPIA, 0.7773 for the FPIA versus bioassay, and 0.7779 for HPLC versus bioassay. The FPIA technique was the easiest and fastest of the three methods; FPIA and HPLC were the most accurate.

Biological Assay↗

Comparative study of postmortem barbiturates, methadone, and morphine in vitreous humor, blood, and tissue.

With the introduction of radioimmunoassay (RIA) techniques, it has become toxicologically possible to determine drug concentrations in postmortem vitreous humor. This study demonstrates and confirms this toxicological feasibility. In 49 medical examiner's drug related cases, postmortem tissue levels of morphine, barbiturates, and methadone were compared to the vitreous humor.

Autopsy↗

Immunofluorescence detection of drugs in postmortem tissues: a new technique with potential for assessment of drug influence in cause of death.

This report describes a new technique, immunofluorescence, for the detection and possible characterization of drug content in postmortem tissues. By using antisera generated against a drug-protein conjugate, the stabilization of tissue-sequestered drug is accomplished by incubation of fresh frozen sections of tissue with dilute solutions of rabbit anti-drug antibodies. Secondary incubation with a fluorescence-labeled anti-rabbit immunoglobulin labels these points of sequestration. Tissue sections so stained are examined by fluorescence microscopy. In studies with rats given graded doses of morphine sulfate, there were discernible differences in tissue binding of morphine in brain sections from animals treated "therapeutically," fatally, and chronically. Extension of these studies to human autopsy material is anticipated and potential problems are discussed. This technique offers the forensic toxicologist the potential for evaluating the drug content of tissues in situ.

Animals↗

A study of the myocardial depressant factor and its relative influence in drug/alcohol mortality.

A shock factor, a low molecular weight peptide, has been isolated from postmortem blood. High levels of this peptide, which depresses the myocardium, were seen in cases where drug overdose or alcoholism, or both, were the cause of death. An elevated myocardial depressant factor (MDF) level also demonstrated in a fire victim and a patient in cardiogenic shock. The peptide analysis was accomplished by using an isolated cat papillary muscle followed by paper chromatographic confirmation. Postmortem electrolytes, alcohol, and various toxic agents were eliminated as causes of myocardial depression in the isolated cat papillary muscle assay. The presence of elevated MDF levels may be significant in the overall death process.

Accidents↗

Evaluation of the Abuscreen for methadone.

The increased use and abuse of methadone in recent years has posed a problem of both its identification and quantitation in body tissues. Recent development of a radioimmunoassay for methadone appears to have solved the problem. In our hands the assay was extremely sensitive and specific. It also appears to be an excellent tool when quantitative estimates are to be obtained. Although it initially appears to be relatively expensive, the time saved in doing a complete tissue distribution equalizes the cost. It is hoped that other radioimmunoassays currently under development will prove as satisfactory.

Adult↗

A method to obtain maternal-fetal plasma samples using a microsampling technique in the rat: transplacental passage of cefoxitin.

A microsampling technique that allows taking blood samples from the umbilical vein of the pregnant rat is described. Such techniques are needed in order to allow pharmacokinetic and embryo exposure to be correlated with teratogenic endpoints. Cefoxitin was administered intravenously (300 mg/kg) into tracheotomized, pentobarbital anesthetized dams on day 21 in gestation. Blood samples were collected via the carotid artery from the dam and the umbilical vein of the fetus at designated times. Up to three samples of 20 to 30 microliters each, were taken from individual fetuses at 20-min intervals. With few exceptions, fetal cefoxitin concentrations were homogeneous at each sampling period. Fetal concentrations were low compared to maternal concentrations as seen by the small fetal/maternal area under the curve ratio (0.053 +/- 0.006).

Animals↗

The determination of propoxyphene, norpropoxyphene, and methadone in postmortem blood and tissues by high-performance liquid chromatography.

This paper describes the quantitative analysis of propoxyphene (PPX), its major metabolite, norpropoxyphene (NPPX), and methadone (METH) in blood and tissue specimens taken at autopsy in cases of suspected drug ingestion. Specimens are extracted into an organic solvent, back-extracted into acid, then reextracted into organic solvent and evaporated to dryness. The reconstituted extracts are subjected to analysis by reversed-phase ion-pair chromatography. The method is linear from 0.1 to 10 mg/L. Recoveries from blood are 86%, 93%, and 91% for PPX, NPPX, and METH respectively. Within-run coefficients of variation are 4.5%, 4.8%, and 2.6% and day-to-day coefficients of variation are 4.7%, 6.8%, and 3.7% for PPX, NPPX, and METH respectively at 1.0 mg/L for each drug.

Chromatography, High Pressure Liquid↗

The production of amitriptyline from nortriptyline in formaldehyde-containing solutions.

The stability of nortriptyline in aqueous solutions containing various concentrations of formaldehyde was investigated. Amitriptyline, as a reaction product, was determined by gas chromatography/mass spectrometry (GC/MS) in these experiments. Factors that may contribute to this phenomenon, including pH, formaldehyde concentration, and incubation time were evaluated. At 40% (v/v) formaldehyde concentration and pH 4, there was a 68% decrease in nortriptyline concentration along with a concomitant formation of amitriptyline after 24 h. The N-methylated product was responsible for 48% of the total tricyclic drug present. The data also clearly indicate that the formation of amitriptyline is favored at elevated pH.

Amitriptyline↗

Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin.

The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

Animals↗