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Biomedical subjects

E Poulsen

Publications and source records attributed to E Poulsen.

At least 19 recordsLinked to original sources
PubMed1999

Cellular effects of heparin on the production and release of tissue factor pathway inhibitor in human endothelial cells in culture.

Tissue factor pathway inhibitor (TFPI), the major downregulator of procoagulant activity of the tissue factor-factor VIIa complex (TF. FVIIa), is synthesized and constitutively secreted by endothelial cells (ECs). Here we describe the in vitro effects of heparin on the cellular localization, gene expression, and release of TFPI in human ECs in culture. Both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH; Fragmin) time-dependently induced a significant enhanced secretion of TFPI, paralleled by a redistribution and increase of TFPI on the cell surface and a decrease of intracellular TFPI. Immunogold electron microscopy showed the presence of clusters of TFPI, both on the plasmalemma proper and within cell-surface opened caveolae/enlarged caveolar profiles. Activation of FX by TF. FVIIa on ECs treated with endotoxin was inhibited by both heparins but to a higher extent by LMWH. Inhibition of protein synthesis by cycloheximide did not reduce the release of TFPI induced by heparin. Long-term incubation (48 hours) resulted in a time-dependent enhanced production of TFPI. After the first 4 to 8 hours, depletion of intracellular TFPI was observed, more significantly with UFH. Northern blot analysis of TFPI mRNA also showed a decrease of the 1.4-kb transcript after 4 hours of incubation with UFH, followed by recovery and an increase over the control level after 24 hours. Incubation of ECs with phorbol ester (PMA) significantly enhanced the secretion of TFPI and increased its activity on the cell surface, probably by preventing invagination of caveolae. Heparin-stimulated release of TFPI decreased significantly in the presence of PMA to a level that was 2. 4 times lower than the expected additive value for PMA and UFH separately. Pretreatment of ECs with PMA suppressed a subsequent response to heparin. Altogether, our results suggest that the heparin-induced release of TFPI might involve a more specific mechanism(s) than the previously hypothesized simple displacement of TFPI from the cell surface glycocalyx. We assume that the increased secretion and redistribution of cellular TFPI induced by heparins in ECs in culture can play an important role in the modulation of the anticoagulant properties of the endothelium.

Cell Line↗
PubMed1993

Risk assessment for people exposed from different environments.

After the identification of the hazardous intrinsic properties of a carcinogen an attempt is made to estimate, if possible, the potency of the carcinogenic effect. For the evaluation it is, furthermore, of interest to know the genotoxic properties of the chemical. The next step would be to try to estimate the potential exposure for people in different environments. This could be intake from use of it as an additive in food or occurrence as a contaminant in food, drinking water, soil or air. The air exposure might come from contaminants in the working environment, in-door air or ambient air. The outcome of the hazard and exposure assessments would not be the only factors in a risk assessment or suggested limit values. Other factors might be the political-administrative background coming from different legal systems, even in the same country, which might apply different safety ambitions. This might result in the application of different risk levels (1:1 million, 1:10 million) or different safety factors, if that approach is used for non-genotoxic animal carcinogens.

Animals↗
PubMed1992

gamma-Glutamylaminotransferase and transglutaminase in subcellular fractions of rat cortex and in cultured astrocytes.

The subcellular distribution of gamma-glutamylamino-transferase (EC 2.3.2.2) and transglutaminase (EC 2.3.2.1) has been investigated in rat brain tissue fractionated by a centrifugation and sedimentation technique. Neither of these enzymes was enriched in the synaptosomal fraction. Comparing the in vitro grown astrocytes with synaptosomes, we find that both of these enzymes may possibly be more important in the glial element of the synaptic region. gamma-Glutamylaminotransferase is most abundant in capillaries, confirming previous reports.

Animals↗
PubMed1989

Influence of legislation in toxicology.

The influence of toxicology on legislation is quite clear in countries where chemicals are regulated by the authorities. There is normally a toxicological evaluation--in addition to other considerations--behind sales and use permissions and the levels that are accepted in food, air, water, etc. How does legislation affect toxicology? If there is no legislation, then clinical and forensic toxicology will be the most used toxicological disciplines (accidents and other cases of poisoning). The more sophisticated and restrictive the legislation becomes, the more toxicology is used not only to permit the use of chemicals but also to ban them. In addition, legislation for the protection of experimental animals has a profound influence in toxicology and accelerates the use of in vitro and other alternative methods. This paper discusses whether countries in the "developed" world are overdoing it, thereby maybe hampering the essential use of chemicals in the developing countries.

Animal Testing Alternatives↗
PubMed1986

Inhibition of antipyrine elimination by disulfiram and cimetidine: the effect of concomitant administration.

We investigated the effect of concomitantly administered disulfiram and cimetidine on antipyrine elimination. On day 1, 2, 4 and 6 of two periods of 6 days one sample antipyrine saliva clearance (APC) was measured in nine healthy volunteers. From day 2 to 6 of period I disulfiram 400 mg day-1 was administered and on day 5 and 6 cimetidine 1000 mg day-1 was added. In period II only cimetidine was given (on days 5 and 6). On day 4 of period II APC was increased 1.3 fold, probably due to self-induction by repeated antipyrine administration. Taking this into account disulfiram and cimetidine separately decreased APC 0.64 and 0.70 times, respectively. When both inhibitors were given APC was reduced 0.52 times. The results suggest that the effects of cimetidine and disulfiram on antipyrine elimination are additive.

Adult↗
PubMed1985

Mutagenicity of flour from the palmyrah palm (Borassus flabellifer) in Salmonella typhimurium and Escherichia coli.

Flour from the young shoots of the palmyrah palm (Borassus flabellifer) was tested in Salmonella typhimurium, strains TA98 and TA100 (Ames test) and Escherichia coli, strains WP2, WP2uvrA, CM881 and CM891. The flour was tested in two forms: boiled and raw. Both forms showed dose related mutagenic responses in the basepair substitution sensitive strains TA100 and Escherichia coli WP2uvrA, CM881 and CM891. The flour from boiled palmyrah shoots exerted a somewhat stronger mutagenic effect on TA100 than flour from the raw shoots. This investigation adds mutagenicity to the wide range of biological effects of palmyrah flour already described (induction of malignant lymphomas, immunosuppression, neurotoxicity and clastogenicity).

Animals↗
PubMed1984

Animal feeding study with nitrite-treated meat.

In order to detect possible formation of carcinogenic N-nitroso compounds from nitrite and nitrosatable compounds in meat, studies were carried out with 70 male and 140 female F0 rats, divided into six groups, and 60, 100, 70, 60, 60 and 66 of their male and female offspring. One control group received casein and other groups chopped pork as the sole protein source (45%, mass/mass) on a fresh basis, either salted (sodium chloride) or not. For test groups, nitrite was also added to the meat before autoclaving and storing the diet and represented mass fractions of 200, 1 000 and 4 000 mg/kg, as sodium nitrite. The results do not demonstrate any effect on reproduction and no significant carcinogenic effect was revealed. However, an observed tendency toward an increased number of tumour-bearing rats in the highest dose group, plus the possible formation of carcinogenic N-nitroso compounds in nitrite-treated meat products, led to a recommendation to reduce the use of nitrite. Results from a concomitant study demonstrate that it is possible to produce many cured-meat products with the addition of only 50 mg/kg nitrite.

Animal Feed↗
PubMed1980

Use of nitrates and nitrites as food additives in Nordic countries.

An account is given of the presently permitted use of nitrates and nitrites as food additives in Denmark, Finland, Norway and Sweden. Nitrate permitted to be added to milk for the production of solid, semisolid and mould cheeses at levels of 150-200 mg/l potassium nitrate. Due to the potential formation of especially nonvolatile N-nitroso compounds, attempts are made to reduce their use. Nitrates, but not nitrites, are still permitted in certain semipreserved fish products (herring) in Denmark, Finland and Sweden, but it will probably be phased out within a few years. Nitrates are not permitted in meat products in Norway and Sweden, while the use is being reduced in Denmark and Finland. The use of nitrite (175-200 mg/kg meat product of sodium nitrite) is generally permitted as a preservative in meat products in Sweden, Finland and Denmark, while it is more restricted in Norway. Due the potential risk of formation of carcinogenic N-nitroso compounds in the meat and in the organism of the consumer serious attempts are made to reduce the use of all Nordic countries.

Animals↗
PubMed1978

Evaluation of food safety. National and international aspects.

Evaluation of the safety of chemicals in food have created considerable interest within the public, political, administrative, and scientific sectors in many parts o- the world. Political and administrative approaches may vary from country to country depdneing on traditions and cultural pattern. The political aims and goals of our times may be clearly defined, but they are often rather obscure seen from a scientific point of view. Health authorities are supposed to interpret the political intentions and transcribe them into practical administration. The use, by national and international health authorities, of the available scientific and technological knowledge to evaluate the safety of the food in question is discussed.

Food↗