Modulation of lipoprotein production in Hep G2 cells by fenofibrate and clofibrate.

Fenofibrate and other fibrate derivatives are commonly used to treat hyperlipidemia. It is not yet clear how they exert their modulatory effects on plasma lipoproteins. To investigate whether these drugs act on the liver to primarily inhibit very low density lipoprotein production, we utilized the highly differentiated human hepatoma cell line, Hep G2. At concentrations greater than 15 micrograms/mL, fenofibrate caused a 30% decrease in secreted apolipoprotein B (apo B) after 4 days of treatment. Pulse-chase studies demonstrated that this was not due to inhibition of apo B synthesis. Triglyceride synthesis by fenofibrate-treated Hep G2 cells was decreased by 30%, and the amount secreted into the medium was reduced by 50%. At a low concentration of drug (5 micrograms/mL), triglyceride secretion was reduced markedly while apo B secretion remained unchanged. Thus, apo B secretion is less sensitive to fenofibrate than the synthesis and secretion of triglyceride, and may be secondary to changes in the latter. Fenofibrate has also been shown to raise plasma high density lipoprotein concentrations. We found that low concentrations of fenofibrate caused a 20-101% increase in secreted apolipoprotein AI (apo AI), and pulse-chase immunoprecipitation studies showed that this was due to an increase in apo AI synthesis. Fenofibrate was compared to clofibrate to investigate whether their relative effects on lipoprotein production in Hep G2 cells were comparable to their relative effects on plasma lipoproteins. Both fibrates decreased the secretion of apo B to the same extent, but only fenofibrate increased apo AI secretion. Fenofibrate was more effective than clofibrate in inhibiting the secretion of lipids by these cells. Thus, the known effects of fenofibrate on plasma lipoproteins can be attributed to its direct modulation of lipoprotein synthesis in the liver cell. Hep G2 cells may thus be useful in testing the relative efficacy of fibric acid derivatives in vitro.     

Anti-phospholipid and anti-DNA antibodies are not associated with the elevated release of circulatory fetal DNA in pregnancies affected by preeclampsia.

OBJECTIVES: We have previously shown that the levels of circulatory fetal DNA are elevated in preeclampsia and that these increases correspond to disease severity. Several reports have indicated that increased levels of antiphospholipid (anti-PL) and anti-DNA antibodies may be associated with preeclampsia, in particular with the severe forms of the disorder. Since the release of cell-free DNA by the placenta is attributed to some form of cell death or damage and as anti-PL and anti-double-stranded DNA (dsDNA) antibodies have been proposed to lead to placental damage, we have studied the relationship between these parameters in preeclampsia. METHODS: Circulating fetal DNA levels in samples taken from pregnant women with mild (n = 12) or severe (n = 12) preeclampsia and from normal pregnant controls (n = 35) were quantified using a Taqman real-time Polymerase Chain Reaction (PCR) assay. The Anti-PL antibodies (IgG and IgM) were assayed by anticardiolipin ELISA and by commercial anti-beta2-Glycoprotein I (GPI) ELISA kits. Anti-dsDNA antibodies (IgG and IgM) were analyzed by a commercially available anti-dsDNA ELISA kit. RESULTS: No correlation could be drawn with the quantity of circulatory fetal DNA in the samples analyzed and corresponding anti-PL or anti-dsDNA antibody levels. Furthermore, no significant difference existed between the levels of these antibodies in the two study groups and the control cohort. CONCLUSION: Our data suggest that the mechanism leading to the increased release of cell-free circulatory DNA from the placenta does not involve trophoblast damage mediated by these agents. Our analysis also questions the reported involvement of anti-PL and anti-DNA antibodies in preeclampsia.     

Chronische Diarrh?en unter NSAR

Ohne Zusammenfassung     

Dynamics of ablation plume particles generated during excimer laser corneal ablation

Background and Objective: Although the empirical characteristics of ArF excimer laser corneal ablation have been well documented, the exact ablation mechanisms are not well understood. The present paper reports a quantitative analysis of corneal ablation plumes using in situ time resolved laser light scattering and Raman spectroscopy. Study Design/Materials and Methods: Bovine corneas were used as the ArF excimer laser ablation targets. Light scattering data were recorded from the ablation plume as a function of height above the tissue surface and as function of delay time with respect to the ablative ArF laser pulse. Results: Raman spectra of the ablation plume allow identification of the particles as water. Mean plume particle diameters are found to decrease with height, while the particle volume fractions are relatively constant. The total volume of plume particles correlates well with the total volume of water in the ablated corneal tissue. Conclusion: The finding of a non-evolving plume composed of water spherules, combined with the excellent agreement between total volume of water in the plume and the content of water in the ablated corneal tissue, support the concept of photodecomposition or “cold ablation” for corneal tissue during ArF excimer laser ablation. © 1995 Wiley-Liss, Inc.     

Urea rebound and delivered Kt/V determination with a continuous urea sensor

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.