La synthese endogene du cholesterol (CH) a ete etudie chez 81 nouveau-nes, ages de 4 mois (BRAS 1) ou de 11 a 12 mois (BRAS2), afin d'evaluer les effets a long terme d'un supplement de CH sur l'homeostasie du CH. BRAS 1 etait compose de 32 nouveau-nes recevant soit du lait humain (HUM) (6M, 7F), une formule a base de lait de vache (VAC) (6M, 3F) contenant 3.5 mg CH/dl, ou une formule a base de lait de vache modifiee (VACM) (6M, 7F) contenant 13.5 mg CH/dl, afin d'evaluer l'effet du supplement sur les taux de synthese du CH. BRAS2 etait compose de 49 autres enfants recevant soit HUM (11M, 6F), VAC (7M, 12F) ou VACM (6M, 7F) jusqu'a l'age de 6 mois dans le but d'evaluer une hypothese d'impression genetique. Ceci a ete realise en utilisant un design "cross-over" et en montant un defi journalier de 250 g de CH a l'age de 11 mois. Le taux d'incorporation de deuterium, provenant des reserves d'eau corporelle, dans la structure du CH a servi comme indice du taux de synthese fractionnel (TSF) de ce dernier sur une periode de 48 heures. Les niveaux de CH total et LDL etaient considerablement eleves dans HUM en comparaison avec VAC et VACM a l'age de 4 mois. La concentration sanguine du CH etait semblable a 11 et 12 mois. Le TSF etait 4 fois plus eleve dans VAC et VACM relatif a HUM, mais il n'y avait pas de difference entre VAC et VACM a 11 et 12 mois. Cependant, les TSF de 4 a 12 mois ont augmente dans HUM et baisse dans VAC et VACM. Nos resultats indiquent qu'independamment du contenu des dietes, le defi journalier de CH n'as pas eu d'effet considerable ni sur les taux de synthese, ni sur les niveaux de CH sanguin. Ces resultats appuient l'idee que le CH alimentaire n'a que des effets minimes sur le metabolisme a long terme du CH.

Graduation date: 1961

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

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published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Studies of aortic plaque reveal the presence of tissue macrophages filled with cholesteryl esters. To study lipoprotein metabolism of in vivo, maturated human macrophages, I isolated cells from human peritoneal effluent. Population analysis using cytochemistry showed substantial numbers of acid-esterase positive monocytic cells, lymphocytes, leukocytes and erythrocytes. Substantial variation in cell populations existed among patients. Human peritoneal cells degraded low density lipoproteins (LDL) and acetylated LDL (AcLDL) by high affinity, receptor-mediated processes. AcLDL degradation saturated at 15 ug protein/ml and LDL degradation saturated at 11 ug protein/ml. Positive correlation of the percentages of monocytic cells with the degradation values (LDL, r =.710; AcLDL, r =.725) and a degradation assay using cells isolated by Lymphoprep showed that the monocytic cells substantially contributed to the degradation of LDL. AcLDL degradation was calcium independent and inhibited by fucoidin. LDL degradation was calcium dependent and very low density lipoprotein and apoE-containing high density lipoprotein (HDL) competed with LDL for receptor uptake; apoE-free HDL, AcLDL and fucoidin did not reduce LDL degradation. Both receptors were pronase-sensitive and degradation was dependent upon lysosomal activity. ACAT activity analysis showed that pre-incubation of cells with LDL or AcLDL stimulated ACAT activity. ACAT activity was greatest for cells preincubated using AcLDL and fresh medium was necessary to maintain the ACAT activity values beyond 24 hrs. LDL-stimulated ACAT activity declined as time was increased above 24 hrs. Flow cytometry analysis of a total cell population and the Lymphoprep-isolated cells revealed a heterogenous T cell population, the presence of monocyte/macrophages, suggested that some of the cells present were activated and confirmed cytochemistry analysis demonstrating that Lymphoprep concentrated the mononuclear cells. Human peritoneal macrophages formed foam cells when incubated in the presence of AcLDL or LDL for 72 hrs. The formation of foam cells in the presence of LDL was dependent upon cell exposure time to the medium. Foam cell formation in the presence of LDL was accompanied by dense vacuolization and in the demonstrated absence of the oxidation of LDL the oil red O stainable material collected outside the vacuoles.

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