Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose.

We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 micrograms cholecalciferol/d for 14 d and were subsequently studied for a further 88 d. Two subgroups of eighteen rats each were fasted for 3 d immediately after treatment (days 14-17) and at the end of the study (days 98-101). During treatment, plasma cholecalciferol increased rapidly to reach a steady-state. Plasma 25(OH)D and adipose tissue cholecalciferol increased linearly for 1-2 d after treatment. Serum Ca and inorganic phosphate also increased. Subsequently half-lives of plasma cholecalciferol and 25(OH)D, and perirenal and subcutaneous adipose tissue were: 1.4, 22.5, 97.5 and 80.9 d respectively. Fasting, as compared with ad libitum feeding, caused increased plasma free fatty acids, weight loss up to 14% and increased adipose tissue cholecalciferol (nmol/g wet weight). It did not affect plasma cholecalciferol immediately after cholecalciferol treatment, but raised plasma 25(OH)D. Fasting at the end of the study decreased plasma cholecalciferol and increased plasma 25(OH)D. We conclude that orally-administered cholecalciferol rapidly accumulates in adipose tissue and that it is very slowly released while there is energy balance. Fasting causes preferential loss of triacylglycerols from adipose tissue, as opposed to cholecalciferol, but nevertheless augments plasma 25(OH)D. Adipose tissue may act as a 'buffer to functional vitamin D status' by preventing, to a certain extent, unregulated production of 25(OH)D from dietary vitamin D, and by slowly releasing vitamin D under fasting conditions.

Apolipoprotein-E polymorphism in Curacao newborns - abstract

Apolipoproteins (apo)E (2) and E (4) are associated with disease development at later age. In Caucasians, homozygosity for apo-E (2) (apo-E/E) occurs in over 80 percent of patients with familial dysbetali-poproteinaemia (prevalence: 0.04 percent). Subjects with apo-E/E have higher cholesterol, both LDL and total, than subjects with the common apo-E/E genotype. High prevalence of apo-E/E in patients with Alzheimer's disease connects apo-E genotype to neuro-degenerative disease development. Little is unknown on apo-E polymorphism in Black populations. Using molecular biological techniques, we determined apo-E genotypes of 234 consecutive cord blood samples in Curacao (The Netherlands Antilles). Forty per cent of babies born during the period of November 1992 - February 1993 were screened. Found and expected Curacao apo-E genotype distributions were not significantly different. Found Curacao apo-E genotype distribution was not different from Dutch, but differed in Nigerians and US-Blacks (p<0.0001). Genetic differences between Curacao and Nigeria/US-Blacks agree with different haemoglobin C prevalences. It remains to be established to what extent apo-E polymorphism contributes to atherosclerotic and neurodegenerative disease development in Curacao (AU)

Low sickle-cell linoleic acid content is related to young erythrocyte age - abstract

Erythrocyte (RBC) fatty acids (FA) and polyamines were determined in subjects with HvM (n=29), HbAC (3), HbAS (41), HbSC (25) and HbSS (19). FA of plasma cholesterol esters (CE), plasma phosphatidylcholines (PC), RBC PC, and plasma and RBC PC-species were studied in subgroups. RBC of patients with HbSS and HbSC had abnormal FA, PC-FA, PC-species and polyamines. There were no major differences in plasma CE-FA, PC-FA and PC-species. Low 18:2U6 in RBC, RBC PC and RBC PC-species of patients with HbSC and HbSS are related to RBC polyamines. Low RBC 18:2U6 is almost stoichiometrically compensated for by higher stearic and palmitic acids. Circulating RBC from patients with HbSC and HbSS have normal total polyunsaturated FA with 20 carbons or more. Low RBC 18:2U6 of patients with HbSS and HbSC is rather related to young RBC-age (RBC polyamines) than to diet (plasma CE-FA). Their rapid RBC turnover causes incomplete RBC-FA exchange with plasma species (AU)

Effects of monocytic products, recombinant interleukin-1, and recombinant interleukin-6 on glycosylation of alpha 1-acid glycoprotein: studies with primary human hepatocyte cultures and rats.

Changes in the carbohydrate moieties of acute-phase glycoproteins (APGPs) often accompany the increase in their secretion by the liver during inflammation. In this study, we investigated whether factors known to regulate APGP gene expression are also involved in the altered glycosylation. For this purpose, the glycosylation pattern of alpha 1-acid glycoprotein (AGP) as secreted by human hepatocytes, cultured in the presence and absence of dexamethasone and monokines, was studied by crossed affino- (concanavalin A) immunoelectrophoresis (CAIE). The monokines rIL-1 and rIL-6, in the presence of dexamethasone, both stimulated AGP secretion and caused a change in glycosylation towards an increased Con A reactivity, including the appearance of two strongly reactive forms (D and E) normally not present. Dexamethasone alone did not influence either process. When tested in vivo in rats, rIL-6 also induced an increased presence of Con A-reactive forms of AGP in serum. In conclusion, the changes in secretion and glycosylation of AGP as seen during inflammation seem to be mediated by the same factor(s).

Relation between acute-phase proteins and enhanced bleomycin-induced pulmonary fibrosis in the rat.

Intratracheal application of Bleomycin (Bleo) in rats induces interstitial pneumonitis followed by progressive fibrosis. As the presence of high levels of acute-phase proteins (= reactants = APR), especially alpha 2-macroglobulin of the rat (alpha 2M), enhances liver fibrosis, we investigated whether this phenomenon also occurs in rats with Bleo-induced lung fibrosis. The experiments showed that this is the case; lung fibrosis assessed by measuring hydroxyproline, hexosamine, and prolyl-4-hydroxylase was enhanced when just before Bleo application an acute-phase reaction was induced. This effect can be explained by the inhibitory effect of alpha 2M on collagenase. The experiments showed a significant positive correlation between alpha 2M and parameters of fibrosis. This is especially the case in the third week after Bleo application. Bleo itself does not induce a strong acute-phase reaction, notwithstanding the pneumonitis during the first weeks. The increased fibrosis is accompanied by progressive ventilatory disturbances demonstrated by high arterial pCO2 and low pO2. In patients undergoing Bleo treatment, varying levels of APR can be expected, and this could explain the rapid development of fibrosis in individual cases.

Influence of liver isoferritin profile on quantitative measurement of total ferritin protein in human liver, with emphasis on iron overload.

Ferritin was isolated from normal human liver and from iron-loaded human liver by gel chromatography and by ultracentrifugation. From each of these ferritin batches several isoferritin fractions were isolated by preparative isoelectric focusing. It was our aim to have at our disposal isoferritin fractions with relatively large pI ranges but distinctly different isoferritin profiles on analytical isoelectric focusing. These fractions were compared for their immunoreactivity. The total protein in the isoferritin fractions was measured by the nitrogen content. The immunoreactivity of the isoferritin fractions was measured as the ratio of the reaction in immunoassays to the nitrogen content of these fractions. We used radial immunodiffusion and enzyme-linked immunoassay to measure immunoreactivity. The immunoreactivity did not change obviously with the isoferritin composition of the isolated fractions. It is concluded that pathological changes in the isoferritin composition that might occur in liver ferritin during iron overload does not significantly influence the quantitative measurement of liver ferritin protein by immunological methods.