PubMed Health⌕ Search

Biomedical subjects

D Neubert

Publications and source records attributed to D Neubert.

At least 127 records · Page 7Linked to original sources
PubMed1986

Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via placenta and milk, and postnatal toxicity in the mouse.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was found to be efficiently transferred to mouse neonates and offspring by lactating mothers. During the first 2 postnatal weeks the pups received doses of TCDD via the milk which were, on a body weight basis, similar to those which had been administered prenatally to their mothers. The distribution of TCDD in the offspring (high in liver, low in other tissues) was similar to that found in the maternal organism. Maternal TCDD levels rapidly decreased during the lactation period while tissue levels in the nursing pups increased, resulting in offspring tissue levels which greatly exceeded those of their mothers at the respective 3-week periods after birth. The postnatal development of pups from mothers treated on days 14-17 of gestation and nursed by untreated foster mothers was studied. Postnatal mortality was increased. Surviving animals did not exhibit visible signs of abnormal development, although the reduced number of pups per litter may have contributed to this apparently normal development. In small rodents excretion into milk constituted a major pathway for the elimination of maternal TCDD. Whether the same holds true for man is still unknown, but the measurement of TCDD levels in breast milk may be an appropriate and practical method for the assessment of human exposure to this substance.

Aging↗
PubMed1986

Pharmacokinetic aspects of drug effects in vitro: effects of serum protein binding on concentration and teratogenicity of valproic acid and 2-en-valproic acid in whole embryos in culture.

Pharmacokinetic studies were performed in connection with culture experiments. Using the technique of cultivating whole rat embryos of the early postimplantation stage, we measured the concentration of valproic acid (VPA) and 2-en-VPA in the culture medium (free and protein-bound form) and in embryonic tissue. The following results were obtained: The concentrations of VPA and 2-en-VPA reached in the embryos were lower than corresponding total concentrations added to the culture medium, but exceeded the free concentrations in the medium. The concentrations of 2-en-VPA found in the embryo were lower than the comparable VPA total levels because of the more extensive protein binding of 2-en-VPA in the culture serum. The percentage of binding to serum proteins decreased with increasing total drug concentrations in the medium; the concentration of the free drug in the medium increased overproportionally with increasing total drug concentrations. Therefore, the free drug concentrations in the medium were not proportional to the dose of the drug dissolved in the medium (for a drug bound to plasma proteins). The concentrations of VPA and 2-en-VPA found in the embryos after incubation in vitro were not proportional to the drug concentrations dissolved in the medium. This result has to be taken into account when dose-response relationships are evaluated. VPA concentrations of 40 micrograms/g wet weight and above in the embryos clearly induced abnormal development in about 30% of the embryos, while 2-en-VPA concentrations as high as 200 micrograms/g embryo (wet weight) were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1986

In vitro studies on the embryotoxic potential of (bis[tri-n-butyltin])oxide in a limb bud organ culture system.

(Bis[tri-n-butyltin])oxide (TBTO) was studied for its toxic potential on prenatal development. The effect of this substance on limb differentiation (mouse embryos) in organ culture was evaluated. In the organ culture system using mouse limb buds, TBTO interfered with morphogenetic differentiation at doses as low as 0.03 microgram/ml (5 X 10(-8)M). This is one of the lowest concentrations of a substance ever found to be active in this in vitro system. The in vitro studies suggest a high embryotoxic potential of TBTO. The low embryotoxicity found in the in vivo studies may be due to limited exposure of the embryos by the original unmetabolized substance.

Abnormalities, Drug-Induced↗
PubMed1986

Results of in vivo and in vitro studies for assessing prenatal toxicity.

Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.

Abnormalities, Drug-Induced↗
PubMed1985

Effects of the cyclophosphamide metabolite acrolein in mammalian limb bud cultures.

Cyclophosphamide must be metabolized by drug-oxidating systems in order to become biologically active. Up to now, it is not known exactly which metabolite is responsible for the teratogenic effects of the drug. Besides aldophosphamide and phosphoramide mustard, the metabolite acrolein must be considered as a possible candidate. We tested this unsaturated aldehyde in a mouse limb bud culture system, since results from in vivo studies are controversial and inconclusive. The following results were obtained: Concentrations of acrolein between 3 and 10 mg/l induce a significant impairment of limb bud differentiation with explants from 12-day-old mouse embryos. Scapula and paw skeleton were more affected than ulna and radius. With limbs from 11-day-old embryos we found similar effects, even at lower concentrations. A contact time of 20-40 min is sufficient to induce abnormal development. It is possible to antagonize the teratogenic effect of acrolein by addition of mesna (300 mg/l) to the culture medium. The abnormalities observed with acrolein under these experimental conditions are clearly different from those seen with hydroperoxy-cyclophosphamide.

Acrolein↗
PubMed1985

Embryotoxicity induced by alkylating agents: left-sided preponderance of paw malformations induced by acetoxymethyl-methylnitrosamine in mice.

The alkylating agent acetoxymethyl-methylnitrosamine (DMN-OAc) triggers preferential left-sided paw defects in mice following IP administration on either day 11 or 12 of pregnancy. Predominantly, ectrodactyly and hypoplasia of the left paws were found. In an organ culture system, using limb buds of 11-day-old mouse embryos, differentiation is severely impaired following addition of 2 microM DMN-OAc to the culture medium. Left and right limbs are equally affected. In contrast, when DMN-OAc is administered in vivo to the dams with subsequent culturing of the limb buds, growth and differentiation of the left limb buds is more affected when compared to the right. Furthermore, DNA alkylation experiments were performed: in vitro, following addition of (14C)-DMN-OAc (2.3 microM) to the culture medium, the DNA alkylation rate of the limb bud DNA is determined. In vivo, following IP administration of 10 mg/kg DMN-OAc to the dams on day 11 of pregnancy, the extent of DNA alkylation of whole-embryo DNA is similar. However, the DNA alkylation rate of separately pooled left and right limb buds exhibits a two-fold difference according to the different teratogenic susceptibility. The results obtained with both in vivo and in vitro systems are consistent with the thesis that a certain amount of DNA alkylation in the tissue of the embryos is the initial step of alkylating agent-induced teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1985

Modification and standardization of the culture of early postimplantation embryos for toxicological studies.

The method of culturing "whole" rat embryos (days 9.5-11.5 of gestation, i.e. at the early stage of organogenesis) as modified and standardized in our laboratory is presented; We have succeeded in using bovine serum as culture medium instead of rat serum as recommended in the original procedure. Experimental conditions are described for obtaining reproducible results; An improved scoring system was developed which, in connection with a computerized documentation, greatly facilitates the evaluation of the data.

Animals↗
PubMed1985

Effect of acyclovir on mammalian embryonic development in culture.

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] interfered with embryonic development in vitro when assessed with the "whole-embryo" culture technique. The "no-observed-effect level" was at 10 microM acyclovir; Minor impairment of embryonic development (retarded development of ear anlagen) was observed in vitro at 25 microM acyclovir in the culture medium. At high concentrations (100 or 200 microM) development of the ear anlagen was largely inhibited. At concentrations of 50 microM acyclovir or higher, additional disturbances of embryonic differentiation in vitro became obvious, resulting in gross structural abnormalities, especially of the brain (telencephalon); Histological examinations confirmed and extended these observations: at 100 microM acyclovir alterations of the neuroepithelium of the ventricles were pronounced, the telencephalon had developed poorly or was almost completely absent, and necroses were seen in the ear anlagen, the maxillary branch and within the somites; In a limb bud culture (mouse embryos, starting with day 11 of gestation) acyclovir interfered with the differentiation of cartilaginous bone anlagen at concentrations of 200 microM and more in the culture medium. A concentration of 100 microM induced no significant effect. Thus, this organ culture system is less sensitive to the action of acyclovir when compared with whole-embryo culture; Contrary to the results achieved with acyclovir, physiological nucleosides (2'-deoxyguanosine and 2'-deoxyadenosine) did not interfere with embryonic development in vitro even at the highest concentration tested (500 microM).

Abnormalities, Drug-Induced↗
PubMed1985

Estimation and removal of baseline drift in the electrocardiogram.

Estimation procedures for baseline drift have been developed using cubic spline, polynomial, and rational functions. In a test set of 50 electrocardiograms (ECGs), each of 2.5-sec duration, baseline stability was significantly improved by application of any of these methods, except rational function approximation. Amplitude histograms of clinical ECGs after subtraction of estimated baseline distortions showed only small baseline variations over the recording period. For a quantitative validation of the estimation procedures, 10 ECGs with artificial baseline drift were constructed and analyzed by correlation and mean square error calculations. From these comparisons, the polynomial approximation emerged as the most efficient method.

Biometry↗
PubMed1984

Effects of angiocardiographic contrast media on the pulmonary circulation in pigs.

In 12 open-chest pigs, mean weight 18 kg, simultaneous beat-to-beat measurements of pressure in the right and left atria and right and left ventricles, and of pressure and flow in the pulmonary artery, were performed before, during and after the injection of 0.8 ml/kg with 10 to 15 ml/s of diatrizoate, ioxaglate and iopamidol as well as mannitol, normal saline solution and own blood into the right atrium, right ventricle and pulmonary artery. Within 5 beats after injection, all determined hemodynamic values reached their maxima of change independent of site of injection and kind of injectate. After 10 to 20 beats, pulmonary resistance diminished, and the reduction was more pronounced and longer lasting the higher the osmolality of the injectate. Hemodynamic changes during the first beats were a result of the rapidly injected volume; longer lasting hemodynamic changes were associated with an osmolality-dependent decrease in pulmonary resistance.

Angiocardiography↗
PubMed1983

Timing of ovulation and implantation in the common marmoset, Callithrix jacchus, by monitoring of estrogens and 6 beta-hydroxypregnanolone in urine.

Urinary estrogen and 6 beta-hydroxypregnanolone excretions have been determined in female marmosets by means of HPTLC. The levels observed in cycling females during implantation and abortion are reported. Hormone analysis revealed a characteristic pattern showing cyclic fluctuations of estrogens and progesterone. Estrogen metabolites increase during the follicular phase up to 1 microgram/ml, the progesterone metabolite level rises to 1.2 micrograms/ml urine during the luteal phase. Maximum values of both are superimposed in many cases. Ovulatory cycles can be monitored by following estrogen and progesterone metabolites in urine samples. Thus ovulation and the onset of pregnancy can be estimated with a precision of +/- 24 h (or less).

17-alpha-Hydroxypregnenolone↗