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Biomedical subjects

M Paolini

Publications and source records attributed to M Paolini.

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

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants.

Red cell free erythrocyte porphyrin and serum ferritin determinations were performed on capillary blood specimens from 63 healthy infants weighing 2500 g or less at birth, during the first week of life, and, from 44 of them, again at 8-10 weeks. Free erythrocyte porphyrin values were high both at 3-7 days (mean 156 microgram/100 ml RBC) and at 8-10 weeks (mean 128 microgram/100 ml RBC). The respective serum ferritin values were also high (mean 226 and 107 ng/ml), excluding a depletion in iron stores. In addition, no correlation was found between free erythrocyte porphyrin and serum ferritin values either at birth or at age 2 months. These findings are consistent with an earlier hypothesis that in the presence of iron stores, the rate of iron release from the stores in low birthweight infants may not be sufficient to maintain optimal erythropoiesis if the demand is accelerated.

Erythrocytes↗
PubMed1982

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↗
PubMed1982

[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↗
PubMed1982

[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↗
PubMed1982

[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↗
PubMed1982

Neonatal screening for congenital adrenal hyperplasia using a microfilter paper method for 17-alpha-hydroxyprogesterone radioimmunoassay. Experience gained from the study of 22,233 cases.

We examined 22,233 infants born in Emilia-Romagna (Italy). Capillary blood samples for 17-OH-progesterone assay were collected on the 3rd, 4th, 5th, 6th or 7th day of life on filter paper of the same type used for the screening of aminoacidopathy and hypothyroidism. 17-OH-progesterone values were determined using a micromethod modified from that of Pang and co-workers. 20 pg/disk was considered as a threshold value and called for a second assay, which was performed in 0.18% of the cases. Pathologic values of 17-OH-progesterone were confirmed in the serum of 4 neonates. In our population the incidence of 21-hydroxylase deficiency was found to be 1 out of 5,558 cases.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Studies on microsomal metabolizing systems for mutagenesis tests. Stability of fortified fractions.

Rat liver S-9 microsomal fractions were fortified with NADP+, G-6-P, and MgCl2 and stored at -80 degrees C and -20 degrees C. At various times aminopyrine demethylase and lipid peroxidation were determined and compared with that of non-fortified fractions. No difference in stability was noted between fortified and not fortified fractions. The known stability pattern of non fortified fractions was confirmed. Lipid peroxidation was found blocked in the fractions stored at -80 degrees C whereas a small release of malonyl dialdehyde proceeded in the frozen state at -20 degrees C, contributing to the loss of activity at this temperature. The use of pre-fortified fractions stored at -80 degrees C is justified.

Aminopyrine N-Demethylase↗
PubMedDate not supplied

Effects of trivalent chromium on hepatic CYP-linked monooxygenases in laying hens.

Chromium is an essential nutrient required for the metabolism of carbohydrates and lipids in humans and many animal species. We evaluated whether feeding laying hens with high levels of different chemical forms of trivalent chromium may affect hepatic metabolizing cytochrome P-450 (CYP)-linked enzymes. Modulation of CYP-dependent monooxygenases (which play a pivotal role in the endogenous metabolism) by Cr(III) was tested using either specific substrates as probes of different CYPs or testosterone as a multi-bioprobe. The CYP-supported oxidases were studied in liver microsomes from laying hens fed with diet supplemented with either 25 or 50 ppm chromium chloride as a yeast or as aminoniacinate. Although at 25 ppm no appreciable effects were observed, at 50 ppm a general inactivation of the recorded monooxygenases (ranging from 34% loss for ethoxycoumarin O-deethylase with chromium chloride to 85% loss for O-deethylation of ethoxyresorufin with either chromium yeast or aminoniacinate) were achieved in the supplemented groups vs controls. The only exception was the O-dealkylation of pentoxyresorufin, which was significantly boosted by both chromium yeast (up to 65% increase) and chromium aminoniacinate (up to 141%). Measurements of the regio- and stereoselective hydroxylation of testosterone used as a multi-bioprobe corroborated the inactivating properties of Cr(III) at the higher dose. Taken as a whole, these findings seem to indicate that high levels of Cr(III) supplementation can substantially impair CYP-catalysed drug metabolism in laying hens.

Animals↗
PubMedDate not supplied

Neonatal screening for 21-hydroxylase deficiency: a microfilter paper method for 17-alpha-hydroxyprogesterone assay.

A micromethod for measuring 17 alpha-hydroxyprogesterone in blood collected on filter paper has been developed. Our method is rapid, easy and has the specificity, accuracy and precision of the radioimmunoassay in whole blood. The method has been applied for screening patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Fifty samples collected on filter paper were assayed by our method, using 125I as tracer, and results were compared with those obtained for the same samples using a tritium tracer. The agreement between the two methods was particularly good in the area ranging from 15 to 100 pg/disc. In one neonate the diagnosis of CAH was made utilizing the microfilter paper method. Our method is a promising screening test for CAH. An indication of the advantages or disadvantages of this type of screening will become available when an adequate number of infants has been examined.

Adrenal Hyperplasia, Congenital↗