Search PubMed⌕ Search

Biomedical subjects

H Nau

Publications and source records attributed to H Nau.

At least 235 records · Page 13Linked to original sources
PubMed1981

Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus.

(1) Following the administration of the highly toxic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant mice, exceedingly low concentrations of this substance were found in the embryo and fetus between gestational days 11 and 18 (between 0.04 and 0.14% of the maternal dose/g tissue). (2) Tissue levels of tCDD in embryos on days 9 and 10 exceeded those of later gestational stages. (3) TCDD levels in fetal livers were 2--4 times higher than those in other fetal organs. (4) Maternal liver contained the highest concentrations of TCDD (4 -10% of the dose/g). A comparison of the results obtained following oral, s.c. and i.p. applications indicated that there was no major first pass effect involved following oral administration. (5) Placenta and other extrahepatic maternal organs exhibited TCDD levels, which were approximately 1, embryos and features 2 orders of magnitude lower than maternal liver concentrations. (6) Good correlation was found between the doses applied (5, 12.5 and 25 microgram/kg) and the tissue levels observed. (7) A single dose of 25 microgram/kg given on day 10 or 5 doses of 5 microgram/kg, 1/day from days 7-11, resulted in higher levels of TCDD in embryos on day 13 than did a singly dose of 25 microgram/kg on day 7; cleft palate was induced at different rates by these treatment schedules.

Animals↗
PubMed1981

Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers.

The pharmacokinetics of valproic acid (VPA) and several metabolites were measured in 11 epileptic mothers and their 12 newborns. VPA was found in higher concentrations in cord serum than in maternal serum [(factor 1.7 +/- 0.6; (n = 6)]. VPA was excreted in the neonates with a mean half-life of 47 +/- 15 hr (n = 8) which is approximately 4 times the mean value found in adult epileptics. Maternal comedication (primidone and phenytoin) resulted in slightly reduced half-lives. The transplacental kinetics of the two main VPA metabolites in blood were similar to those of VPA. The very low levels of VPA in mother's milk (3% of maternal serum concentrations) suggest apparent safety of breast feeding. The [13C]aminopyrine breath test indicated neonatal hepatic enzyme activities which were slightly above those of unexposed neonates, but much below those of neonates which had been exposed to primidone and phenytoin in utero. Six of eight neonates exposed to VPA-monotherapy, but only one exposed to primidone or phenytoin comedication, developed an icterus neonatorum. A number of minor anomalies (four to eight per child) were observed, particularly hernias, diastasis of musculus rectus abdominis and weak abdominal walls. Two children were microcephalic and in another four children the head circumferences were below the 10th percentile. Significant withdrawal symptoms were not observed. Also hypoplasia of the nails and phalanges and facial dysmorphism associated with the "fetal hydantoin syndrome" did not occur in VPA-exposed children except in one case in which primidone had been administered as comedication.

Abnormalities, Drug-Induced↗
PubMed1980

Microassay for primidone and its metabolites phenylethylmalondiamide, phenobarbital and p-hydroxyphenobarbital in human serum, saliva, breast milk and tissues by gas chromatography--mass spectrometry using selected ion monitoring.

A method for the quantitative determination of primidone and its metabolites phenobarbital, phenylethylmalondiamide (PEMA) and hydroxyphenobarbital (free and conjugated) in serum, urine, saliva, breast milk and tissue has been developed. Following the addition of the methyl analogues of primidone, phenobarbital and PEMA as internal standards and of saturated ammonium sulphate, the samples (5--100 microliter) were extracted twice with ethyl acetate--benzene (20:80). The extracts were divided into two equal portions; one portion was ethylated by Greeley's method for the analysis of primidone, phenobarbital and hydroxy-phenobarbital, while the other was trimethylsilylated for the analysis of primidone and PEMA. A gas chromatographic--mass spectrometric system was used for the analysis of the derivatized extracts. Linear calibration curves were obtained in the concentration range studied (between 100 ng/ml and 30 microgram/ml). The recoveries of the drugs were between 80 and 93%. The relative standard deviations were between 3.2 and 5.9% (100-microliter serum samples containing 1 microgram/ml of the drugs). The lower detection limits were found to be between 1.4 and 3.7 ng/ml using serum samples of 100 microliter. These methods have been applied to the study of the placental transfer and neonatal disposition of primidone and its metabolites in the human.

Female↗
PubMed1980

An improved method for the preparation of human fetal and adult hepatocytes.

A method to prepare isolated hepatocytes from the small amounts of liver or liver fragments obtained from the human fetus following therapeutic abortion in early pregnancy is described. The hepatocytes have been characterized by electron microscopy and by their ability to dealkylate the benzodiazepine drug prazepam. The preparation of hepatocytes from a liver sample obtained from a kidney transplant donor is described and discussed.

Cytological Techniques↗
PubMed1979

Studies on cytochrome c oxidase, VII. Isolation and chemical characterization of polypeptide VII.

Polypeptide VII of cytochrome c oxidase was isolated and purified by gel filtration on Bio-Gel P-10 in 10% acetic acid. Automatic Edman degradation of this peptide chain was not successful, because it is blocked at the N-terminus. The amino acid analysis shows a relatively high content of hydrophilic residues (54%). On the basis of this analysis and the apparent molecular weight by sodium dodecyl sulfate gel electrophoresis and gel filtration, a chain length of about 80 residues was calculated. Among the tryptic peptides one blocked heptapeptide was found. Cleavage of this peptide with thermolysin gave two peptide fragments, one of which was not retained on a cation exchange resin. Mass spectrometric sequence determination of this peptide revealed the structure Ac-Ala-Glu-Asp for the N-terminus of polypeptide VII. Treatment with carboxypeptidase A at two different pH values showed that the C-terminal amino acid is isoleucine and the penultimate amino acid is lysine.

Amino Acid Sequence↗
PubMed1978

Quantitative analysis of prazepam and its metabolites by electron capture gas chromatography and selected ion monitoring. Application to diaplacetal passage and fetal hepatic metabolism in early human pregnancy.

Methods have been developed for the determination of the benzodiazepine tranquilizer prazepam and its metabolites desmethyl diazepam, 3-hydroxy-prazepam and oxazepam by electron capture gas chromatography and selected ion monitoring with diazepam as the internal standard. The benzodiazepines were isolated from blood serum or homogenized tissue samples, either by extraction with ethyl acetate or on small Extrelut columns packed with porous silica. The concentrated extracts were directly injected into the gas chromatograph equipped with an electron capture detector. Following trimethylsilylation, analysis on a gas chromatography--mass spectrometry--computer system operated in the selected ion-monitoring mode was performed. Using 50--200 mg (microliter) biological material, concentrations of prazepam and metabolites of 5 ng/g(ml) could be determined with signal-to-noise ratios of greater than 10. Using 1 g(ml) samples, the same signal-to-noise ratios were obtained with 1 ng/g(ml) concentrations. The methods developed were applied to the analysis of the diaplacental transfer of prazepam and desmethyl diazepam in early human pregnancy. Furthermore, prazepam metabolism in human fetal liver and cell cultures was studied.

Cells, Cultured↗
PubMed1977

Quantitative analysis of trifluoroacetic acid in body fluids of patients treated with halothane.

A simple procedure for the quantitative analysis of trifluoroacetic acid (TFA) in urine and serum from patients narcotized with halothane is described. This involves addition of sodium hydroxide to the body fluid, evaporation of the aqueous phase and esterification of TFA in concentrated sulphuric acid with 2,2,2-trichloroethanol. The gaseous phases above the reaction mixture were then analyzed by gas chromatography with a nickel-63 electron-capture detector. The detection limit was 1 microgram of TFA per mililitre of body fluid (200 microgram of body fluid are analysed) and the relative standard deviation was +/-6%. Patients treated with ethrane, another commercial anaesthetic, did not produce any detectable TFA.

Anesthesia↗