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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 325 records · Page 18Linked to original sources

Effects of fasting on the hypoxia-induced erythropoietin production in rats.

In order to test the hypothesis that the early cessation of erythropoietin (Ep) production during hypobaric hypoxia is induced by lowered food intake, we have compared the plasma Ep titer of rats after exposure to continuous hypoxia (42.6 kPa = 7000 m altitude) for 4 days with that in fed or fasted rats after exposure to discontinuous hypoxia. We found that plasma Ep was rather low after 4 days of continuous hypoxia. However, the Ep titer significantly rose again, when rats were maintained normoxic for 18 h and then exposed to repeated hypoxia for 6 h. Because this was also found in rats which were deprived of food during the normoxic interval and the second hypoxic period, we conclude that the fall of the Ep titer during continuous hypoxia is not primarily due to reduced food intake. In addition, our findings show that fasting per se lowers the Ep-response to hypoxia in normal rats but not exhypoxic rats.

Animals↗

Stability of microsomal mono-oxygenase during incubations for the liver microsomal assay with S9 fractions of mouse liver under various inductions.

Aminopyrine-N-demethylase and p-nitroanisole-O-demethylase activities were determined in incubation mixtures for the liver microsomal assay at time zero and after 1 h of incubation in the conditions for the mutagenic assay. The experiments were performed with the S9 liver fraction of mice in the basal state and induced with sodium phenobarbital, beta-naphthoflavone or both. Lipid peroxidation was also determined. The experiments were repeated with female mice and also in the presence of styrene, as an example of a xenobiotic substance. The activity of pNAD was much more stable than that of APD in all the conditions tested. The pattern of stability, however, was similar for the two activities: more stable than controls with S9 fractions from beta-NF-induced mice, less stable than controls in PB-induced mice, intermediate between controls and PB-induced mice in those with combined induction by PB + beta NF. Styrene 50 mM in the incubation mixtures led to a marked inactivation of enzymic activity, similar in all cases and reaching about 90% in 1 h. S9 fractions from female mice gave enzymes slightly more stable in almost all cases. Lipid peroxidation was appreciably more elevated in basal than in induced animals. It was concluded that, for a mutagenesis test on an unknown xenobiotic, S9 fractions from mice following PB and beta-NF induction are to be preferred from the point of view of activation.

Aminopyrine N-Demethylase↗

Genetic and biochemical studies on perchloroethylene 'in vitro' and 'in vivo'.

Perchloroethylene (PCE) was tested in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension tests with and without a mammalian microsomal activation system (S9) and 'in vivo' by the intrasanguineous host-mediated assay. In addition, enzyme alteration studies were performed in mice non-pretreated or pretreated with phenobarbital + beta-naphthoflavone. PCE did not induce any genetic effect either 'in vitro' or 'in vivo'. In the suspension test, PCE was more toxic without metabolic activation and less toxic with mammalian microsomal activation. The enzymatic determinations showed an increase of the aminopyrine demethylase activity and of the level of cytochrome P-450.

Aminopyrine N-Demethylase↗

Mutagenicity of 3 structurally related epoxides, with defined stereochemical configuration, in Saccharomyces cerevisiae and in V79 Chinese hamster cells.

3 structurally related epoxides, 3,4-epoxycyclohexene, trans-1,2,3,4-diepoxycyclohexane and trans-3,4-epoxycyclohexane-r-1,trans-2-diol (anti isomer) were tested for their ability to induce both point mutation, mitotic gene conversion and recombination in a diploid strain (D7) of the yeast Saccharomyces cerevisiae, with and without a mammalian microsomal activation system, and the formation of 6-thioguanine-resistant mutants in V79 hamster cells. Genetic effects were related to the alkylating properties of the epoxides, as measured by alkylation of 4-(p-nitrobenzyl)pyridine (NBP). Of the 3 epoxides, only 3,4-epoxycyclohexene, characterized by the highest reactivity towards NBP, induced all genetic effects in both test systems. A marginal activity was shown by trans-1,2,3,4-diepoxycyclohexane only in the yeast. The lack of genetic activity of the anti isomer of 3,4-epoxycyclohexane-1,2-diol, in spite of the formal similarity of its functional groups with those present in mutagenic polycyclic arene epoxydiols, was attributed to the dramatic reduction of lipophilicity of the molecule.

Animals↗

Cytochrome P-450 factors determining synthesis in strain D7 Saccharomyces cerevisiae. An alternative system to microsomal assay.

Certain aspects of cytochrome P-450 induction were studied in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in order to obtain cells containing a high level of metabolizing enzymes. The highest level of cytochrome P-450 was reached during the logarithmic growth phase in a 20%-glucose liquid medium. Yeast cells harvested in these conditions were used in the mutagenesis test with dimethyl nitrosamine (DMNA) as a positive control and with styrene (Sty). Both substances gave positive results, whereas Sty never showed any mutagenic activity in the conventional test with stationary growth phase cells and external metabolic activation. The test with cells from the logarithmic growth phase is proposed as a possible alternative to the liver-microsome assay, and its reliability is discussed.

Animals↗

Renal mesangial cell cultures as a model for study of erythropoietin production.

Mesangial cells derived from isolated glomeruli of rat kidney were grown as homogeneous cell lines in culture. They released, into the culture medium, erythropoietin that had free terminal galactosyl residues and was therefore not active in vivo. The production of erythropoietin by these cells was significantly enhanced by either lowering the PO2 in the incubation atmosphere or by adding cobalt chloride to the culture medium. Therefore, mesangial cells in culture may be considered as an in vitro system in which the regulation of erythropoietin production can be studied under well-defined conditions.

Animals↗

Extraction of erythropoietin from isolated renal glomeruli of hypoxic rats.

We investigated whether erythropoietin (Ep) can be extracted from renal glomeruli of hypoxic rats. Hypoxia was induced in a hypobaric chamber at 0.42 atmospheres for usually 6 h. Glomeruli were isolated with a sieving technique from kidneys that were flushed free of blood. Ep activities in glomeruli homogenates were determined in the fetal mouse liver cell assay and in the hypoxia exposed mouse assay. We found in vitro erythropoietic activity of glomerular extracts, which increased about 25-fold during hypoxia. Incubation of the extracts with anti-Ep serum abolished the activity. Its binding characteristics on Wheat germ lectin. Ricinus communis lectin and DEAE-cellulose suggested that glomeruli contained Ep precursor(s) that lacked terminal sugar residues. Such an incomplete carbohydrate portion seems also compatible with the finding that glomerular extracts did not stimulate erythropoiesis in hypoxia exposed mice.

Animals↗

A new candidate for the regulation of erythropoiesis. Insulin-like growth factor I.

The effect of pure human insulin-like growth factor I (IGF I) on the colony formation of late stage erythroid precursor cells (CFU-e) from fetal mouse liver and adult bone marrow was studied in a serum-free culture system. We found that IGF I in physiological concentrations stimulated erythroid colony formation. The combined effect of IGF I and erythropoietin was smaller than the sum of their single effects. The number of colonies induced by IGF I was linearly dependent on the number of plated cells. Our results indicate that IGF I is the first clearly defined mitogen that stimulates the late stages of erythroid differentiation independently of erythropoietin.

Animals↗

Effect of repeated ether anesthesias on levels and stability of monooxygenase system activities of mouse liver.

A short diethyl ether anesthesia before the three injections to induce xenobiotic metabolizing monooxygenase in mice for the preparation of liver S-9 fraction used in mutagenesis test in vitro does not negatively alter the biochemical properties of the activating system and gives unchanged genetic results. Instead, the use of more prolonged ether anesthesia also at the day of the sacrifice, results in less active and less stable enzymes in the S-9 fraction, which can lead to altered genetic results.

Aminopyrine N-Demethylase↗

[Levels of xenobiotic metabolizing enzyme activities of xenobiotic tissue in different animal species].

Aminopyrine-N-demethylase, p-nitroanisole-O-demethylase and lipid peroxidation were determined in liver postmitochondrial fractions (S-9) of mice in the basal state and after induction with beta-naphtoflavone, sodium phenobarbital, or both the inducers. The two activities were similar in their response to all inductions: meanly, 1,2 times with beta-NF, 2,0 times with Na-PB, 5,8 times with Na-PB+ beta-NF. Lipid peroxidation was sensibly more active in basal animals with respect to that with induction. The results are discussed in a partial review of the sector literature, which deserves still much work to be completed.

Aminopyrine N-Demethylase↗

[Genetic activity of 1,2-dichloroethylene. A). In vitro studies].

1,2-dichloroethylene cis and trans were tested for their ability to induce point mutation, mitotic gene conversion and mitotic recombination in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in a suspension test with and without a mammalian microsomal activation system. In this test 1,2-DCE cis and trans were toxic but not genetically active even with S9 activation.

Dichloroethylenes↗

[Genetic activity of 1,2-dichloroethylene. B). In vivo studies: effect on microsomal enzymes].

Mutagenicity study "in vivo" (Intravenous host mediated assay) confirms suspension test results with cis- and trans -1,2-dichloroethylene: no genetic effects could be detected. Single and repeated doses of trans-1,2-DCE induced liver aminopyrine demethylase and cytochrome P-450 whereas the cis- isomer decreased them. Similar results were obtained after induction with phenobarbital + beta-Naphthoflavone.

Aminopyrine N-Demethylase↗