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Biomedical subjects

D Neubert

Publications and source records attributed to D Neubert.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1983

Interference of acetoxyalkyl-nitrosamines with limb bud differentiation in organ culture.

alpha-acetoxynitrosamines have been used as model compounds to study biological activity of N-nitrosamines. After hydrolytic cleavage they yield an "active intermediate" (the hydroxynitrosamine) which presumably also arises as metabolite of N-nitrosamines. We tested eight N-nitrosamines mono-substituted at the alpha-carbon with an acetoxy group for their teratogenic potential in a mouse limb bud culture system. The following results were obtained: 1. The methyl compound (MOAc-MNA) - a derivative of dimethynitrosamine - proved to be the strongest teratogen in this group of chemicals. 2. The tertiary-butyl derivative - releasing a carbonium ion of low chemical reactivity - possessed the lowest activity in our test system. 3. The primary alpha-acetates with unbranched side chains (POAc-MNA or BOAc-MNA) were more active than the corresponding derivatives with branched side chains. 4. The secondary alpha-acetate (EOAc-ENA) was clearly less active than the primary alpha-acetate (EOAc-MNA). 5. A teratogenic potential could also be demonstrated in the organ culture system with the cyclic derivative: N-nitroso-alpha-acetoxy-pyrrolidine (NAPYR). 6. With the use of limb buds from 12-day-old mouse embryos the explants showed the highest susceptibility to the teratogens on the first day of culture. No effect could be produced if the substances were added to the culture medium at the third day of culture or later. 7. When initiating the culture with limb buds from 11-day-old mouse embryos the concentrations needed to induce typical effects were lower than those tested with 12-day-old explants. 8. Typical and pronounced impairment with morphogenetic differentiation could be induced by MOAc-MNA if the substance was present in the medium for less than 60 min - the shortest period tested was 15 min. 9. A different abnormality pattern could be induced with the various substances tested. This may partly be explained by a quite different stability of the compounds in the test system. 10. N-Nitrosamines must be expected to be highly teratogenic if they can be "activated" in embryonic tissues. Such an activation into potent electrophilic agents does not occur in rodents under normal conditions. It will be interesting to study if such activity can be "induced" in embryonic tissues of rodents or if it is already present in embryonic tissues of primates.

Animals↗
PubMed1981

Manifestation of carcinogenesis as a stochastic process on the basis of an altered mitochondrial genome.

Computer calculations are used to show the feasibility of a concept which explains the manifestation of a pathological cell function from a latent state by the phenomenon of extrachromosomal inheritance (through the mitochondrial genome) in mammalian cells. A hypothesis is submitted in which this principle is applied to the process of carcinogenesis. According to this concept, the manifestation of a tumor cell--after the initiation stage--entirely depends on stochastic events, i.e., random distribution of mitochondria during cell divisions, with an accumulation of the lesion in a few out of many cells. We feel that this concept comprises a better explanation of many characteristics and peculiarities of the phenomenon of carcinogenesis than do attempts which explain tumor formation as a phenomenon caused by mutation in a nuclear genome. A consideration of the principles presented automatically leads to a number of specific consequences with regard to carcinogenesis. Some of these consequences are discussed. They include: 1. the process of malignant transformation should not be irreversible for all the cells of a progeny; 2. the number of mitochondria in a cell type should be inversely correlated to tumor frequency; 3. the latent period should mainly be determined by the cell division rate and the "extent" of the initiating event; 4. susceptibility to carcinogenesis may be substantially higher if the number of mitochondria per cell line is increasing or decreasing, i.e., during the embryonic and fetal periods; 5. heterogeneous types of cells may arise from a single "initiated" cell, and 6. the process of malignant transformation should not necessarily be confined to one generation of the species. In addition, experimental approaches to support the submitted concept are suggested.

Animals↗
PubMed1980

Estimation of creatine phosphokinase and hydroxyproline in the developing limb: its use in evaluating the effect of teratogens on myogenesis and chondrogenesis.

Forelimbs of mouse fetuses were examined for tissue-specific, drug-induced alterations in their biochemical composition. The activity of the enzyme creatine phospholinase (CPK; to estimate myogenesis) and the content of hydroxyproline (HP; to estimate chondrogenesis) were compared in homogenates of control and treated mouse-fetus forelimbs on day 14 of gestation. In addition, the content of DNA, RNA, and protein was also measured. Injection of 6-aminonicotinamide (6-AN) (15 mg/kg) on day 10 resulted in an overall growth retardation in day 14 fetuses and all biochemical parameters tested were reduced. The ratio of PH:CPK was unaffected by 6-AN treatment. Retinoic acid (vitamin A acid; 100 mg/kg), administered to pregnant female mice on day 10, produced severe forelimb defects and resulted in a signific 10 resulted in an overall growth retardation in day 14 fetuses and all biochemical parameters tested were reduced. The ratio of PH:CPK was unaffected by 6-AN treatment. Retinoic acid (vitamin A acid; 100 mg/kg), administered to pregnant female mice on day 10, produced severe forelimb defects and resulted in a signific 10 resulted in an overall growth retardation in day 14 fetuses and all biochemical parameters tested were reduced. The ratio of PH:CPK was unaffected by 6-AN treatment. Retinoic acid (vitamin A acid; 100 mg/kg), administered to pregnant female mice on day 10, produced severe forelimb defects and resulted in a significant reduction in day 14 forelimb HP and RNA content, without altering CPK, DNA, or protein; thus, the HP:CPK ratio was decreased. These results indicated that 1) 6-AN nonspecifically retards growth and cyto-differentiation in limbs; 2) retinoic acid inhibits synthesis of collagen and RNA; 3) retinoic acid has a differential effect upon chondrogenic and myogenic tissues of the limb, and 4) the comparison of HP content and CPK activity in tissue homogenates is an acceptable method of evaluating teratogenic compounds for selective effects.

6-Aminonicotinamide↗
PubMed1980

Testing for embryotoxicity.

No animal species exists with which the situation in man can be completely mimicked. This also holds true for non-human primates. With animal experiments only certain aspects of the whole complex situation can be analyzed. In order to achieve this successfully, animal species and experimental set-ups have to be chosen carefully to represent the situation existing in humans in as suitable a model as possible. The more the model deviates from the situation existing in humans, the less will be the predictability. It has to be decided, and this is mainly a political decision, what risk is acceptable. Both terms "risk" and "acceptable" have to be specified. Animal studies beyond routine procedures will have to include the use of more and other species (e.g., primates), and in vitro systems adjusted to the special problem to be solved. Today more information is needed on the pharmacokinetic and "toxico" dynamic properties of old and new chemicals. This will supply data on the embryotoxic/teratogenic doses of a substance or on their non-embryotoxic/teratogenic doses relevant to man. A drastic reduction in the number of chemicals pregnant women are exposed to will greatly enhance the chance to perform experiments on the remaining substances successfully and the chance to obtain valid data.

Animals↗
PubMed1980

Significance of organ culture techniques for evaluation of prenatal toxicity.

A discussion of the applicability of in vitro techniques now available for research in prenatal toxicology is presented. Advantages and disadvantages of the various in vitro methods (such as cultivation of preimplantation embryos, whole embryo culture, and organ culture) as applied to various problems of experimental research are described. As a typical example, the experience gained in our laboratory with the organ culture of mammalian limb buds is detailed. Various aspects of the research with this type of organ culture - e.g., different techniques of culturing, extent of differentiation achieved in culture, induction of abnormalities in culture, supplementing the system with drug-metabolizing capacities and means for quantification of the data - are discussed. It is concluded that certain in vitro techniques using mammalian embryonic tissues are very suitable tools for elucidating the mode of action of teratogenic agents, and that they may serve as a "model" for several basic processes also for the situation probably existing in humans. Such organ culture, and other in vitro methods, provide little, if any advantage over in vivo experiments if a "mass screening" of a possible teratogenic potential of chemicals (hazards for the human population) is attempted.

Abnormalities, Drug-Induced↗