Showing papers by "Tilman B. Drüeke published in 1989"

Rapid stimulation of calcium uptake by isolated rat enterocytes by 1,25(OH)2D3.

Abstract: Evidence is accumulating that 1,25(OH)2D3 may stimulate calcium transport from the intestinal lumen extremely rapidly by a mechanism which appears independent of de novo protein synthesis. To investigate this rapid action of 1,25(OH)2D3, the rate of calcium uptake by isolated enterocytes from duodena of young rats was determined in vitro as the uptake of45Ca from 1–15 min. Prior in vitro exposure of cells to 1,25(OH)2D3 (100 pM) for 20 min significantly increased the rate of calcium uptake (p<0.001), an effect unaltered by 50 μM cycloheximide. Incubation with 100 pM 1-alpha-hydroxyvitamin D3 produced the same effect (p<0.01). In contrast, exposure to 10 pM 1,25(OH)2D3, as well as to 100 pM or to 1,000 pM 25-hydroxyvitamin D3 induced no significant change. Because both 1,25(OH)2D3 and starvation may stimulate key enzymes in polyamine metabolism, we investigated the effects of (i) difluoromethyl-ornithine (CHF2-Orn), a specific irreversible inhibitor of ornithine decarboxylase and (ii) varying the timing of feeding prior to sacrifice. Both in vitro CHF2-Orn and feeding prior to sacrifice significantly decreased the baseline rate of calcium uptake (p<0.05) and reduced the effect of 1,25(OH)2D3. Increased duration of starvation significantly increased the baseline rate of calcium uptake (p<0.02) without changing the increment in rate of calcium uptake induced by 1,25(OH)2D3. The study suggests (i) that the early action of 1,25(OH)2D3 on the influx process of intestinal calcium transport may involve a different molecular specificity from that involved in the genomic action of 1,25(OH)2D3 and (ii) that changes in polyamine metabolism may play a part in this process.

Influence of end-stage renal failure on concentrations of free apolipoprotein A-1 in serum.

Abstract: We determined, immunoturbidimetrically, the concentrations of apolipoprotein A-I (apo A-I) (a) in total serum, (b) in total lipoproteins, and (c) in the fraction of d greater than 1.21 kg/L (free apo A-I) in 31 uremic patients (16 on hemodialysis, HD, and 15 with end-stage renal failure, ESRF) and 14 control subjects. The concentration of free apo A-I in serum was significantly increased in both groups of uremic patients (0.27 +/- 0.07 g/L for HD and 0.22 +/- 0.08 g/L for ESRF, mean +/- SD), in comparison with the control group (0.14 +/- 0.04 g/L). The ratio of total apo A-I to high-density-lipoprotein cholesterol was significantly increased in sera from both uremic groups, whereas the apo A-I/HDL-chol ratio of total lipoproteins was similar in all three groups. No apo A-I could be detected in five ultrafiltrates of plasma, even after 100-fold concentration. Analysis of apo A-I isoforms by isoelectrofocusing revealed a significant relative increase in apo A-I3 and a decrease in apo A-I5 isoform in ESRF patients, but not in HD patients. Finally, we found no relationship between serum TG and free apo A-I concentration.

Presence of Apo B48, and relative Apo CII deficiency and Apo CIII enrichment in uremic very-low density lipoproteins.

Abstract: In the present study, lipid and apolipoprotein composition of very low density lipoprotein (VLDL) was analyzed in 39 patients with end-stage renal failure by comparison with 41 healthy subjects. Uremic patients had an increase of serum triglycerides (TG) concentration by comparison with control values. This increase of serum TG was associated with an increase of VLDL which had a normal percent amount of main components. Furthermore a mid-band between VLDL and low density lipoproteins (LDL) on polyacrylamide gel was observed in 22 out of 39 uremic patients but in only 1 out of 41 control subjects. In uremic VLDL Apo B48 was more frequently observed than in control VLDL (p less than 0.05). Furthermore, the content of Apo CII expressed as percent of total Apo C was significantly (p less than 0.001) decreased in uremic VLDL (19.13 +/- 4.54 p. cent) as compared to normal VLDL (23.57 +/- 4.40 p. cent). Apo CIII-O was significantly (p less than 0.001) increased (9.58 +/- 7.19 p. cent vs 5.55 +/- 6.12 p. cent, whereas Apo CIII-1 and Apo CIII-2 distribution was not modified in uremic VLDL. These anomalies were present in uremic patients even when no elevation of fasting serum TG was present. No significant change was observed in uremic patients before their fifth as compared to their first hemodialysis (HD) session, respectively, for any of the parameters studied. Advanced chronic renal failure is associated with a variety of anomalies of TG-rich lipoproteins isolated at d less than 1.006 g/ml which are not reflected by the degree of hypertriglyceridemia and are not corrected by the first four HD sessions.

Diet-induced hyperlipoproteinemia and lipid accumulation within spontaneous arterial lesions in the rat.

Abstract: The extent of diet-induced lipid accumulation evaluated histologically within rat caudal artery lesions, which represent sites of spontaneous intimal injury, was studied in relation to plasma cholesterol and lipoprotein changes in two consecutive experiments: 1) Rats were fed diets enriched with various amounts of cholesterol and saturated lipids from 5 to 12 weeks of age. A large range of values of cholesterolemia was observed at the time of sacrifice, and the more the diet was enriched in cholesterol and saturated lipids, the more the mean of the arterial score, which expressed the extent of lipid deposits within caudal artery lesions, was elevated. Among the biochemical parameters studied, in decreasing order, total cholesterol, LDLchol and VLDLchol were determinant for the arterial score. 2) Rats were fed a diet containing a moderate amount of lipids and the cholesterol concentration in the 3 classical plasma lipoprotein fractions was determined at 1.5, 3 and 6.5 weeks after starting the diet. In this experiment, statistical analysis showed that the degree of lipid accumulation within caudal artery lesions correlated only with the values of VLDLchol determined early (1.5 week) after starting the diet and not with those at the time of sacrifice. However, VLDLchol values correlated with those of LDL and total plasma cholesterol. The data from these two series of experiments suggest that in diet-induced hypercholesterolemia, the intensity of lipid deposits within areas of the arterial wall where spontaneous injury had occurred was related to the values of total plasma cholesterol as reflected both by VLDLchol and LDLchol. An independant effect of one of these lipoproteins cannot be demonstrated since they are correlated with one another.

Parathyroid Hormone and Lipid Metabolism

Abstract: In addition to its well known actions on classic target organs, it has become apparent in recent years that parathyroid hormone (PTH) exerts effects in many other tissues Thus, PTH has also well-defined effects on lipid metabolism The hormone stimulates adipose tissue lipolysis in vitro in the experimental animal (1) as well as in the man (2–4) The administration of parathyroid extract into dogs and into human beings induces an increase in serum free fatty acids (3,5)