How to interpret intratreatment changes in plasma beta-2-microglobulin concentrations.
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T Marsen
Publications and source records attributed to T Marsen.
Correlation of beta-2-microglobulin concentration changes to changes of distribution volume.
Plasma and ultrafiltrate beta-2-microglobulin (B2M) concentrations were determined during hemofiltration (HF) and hemodialysis (HD) in order to evaluate elimination kinetics of B2M. Calculations were done on the basis of plasma-water-concentrations (PWC). Elimination of B2M during HF follows first order kinetics (r = 0.97) and the volume of B2M distribution was calculated to be 17 +/- 2% of body weight. This reflects extracellular volume (ECV). Changes of ECV in HD were induced by weight loss and further provoked by fluid shifts from intra- to extracellular volume and vice versa induced by varying dialysate sodium concentration. These ECV changes were followed by determining inuline in plasma and total dialysate. Changes of B2M concentration correlate well to changes of ECV (r = 0.98). Thus intratreatment concentration changes of B2M in cuprophane dialysis reflect simultaneous changes of B2M distribution volume. This does not exclude the possibility of B2M generation stimulated by dialysis, but proving such effects in vivo will be difficult because of multiple variants, that must be controlled.
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Effects of high-dose medroxyprogesterone acetate and various other steroid hormones on plasma membrane lipid mobility in CAMA-1 mammary cancer cells.
The influence of medroxyprogesterone acetate (MPA) and various other steroid hormones on the lateral diffusion of the fluorescent lipid probe 1-acyl-2-(N-4-nitrobenzo-2-oxa-1.3-diazolyl)-aminocarpropylphos phatidylcholine (NBD-PC) in the plasma membrane of intact mammary cancer cells (CAMA-1 cell line) has been studied by fluorescence recovery after photobleaching technique. Incubation of cells with MPA in serum free medium at ambient temperature for 1 hr led to a significant decrease in the lateral diffusion coefficient of NBD-PC. MPA induced this change over a limited concentration range with 10(-7)-10(-5) mol/l near-maximal or maximal effects, and 10(-8) mol/l exhibiting no effect. Exposure of the CAMA-1 cells to 10(-7) mol/l MPA in undiluted serum induced a significant effect following 1.5 hr of treatment with no increase in effectiveness up to 4 hr of incubation. As compared to MPA, the other steroids tested were less effective or ineffective. The influence on lateral lipid mobility diminished as follows: MPA greater than progesterone greater than 5a-DHT approximately 17 beta-estradiol greater than dexamethasone, and roughly seems to parallel their lipid solubility as estimated by partition coefficients in an n-octanol-water system. Any involvement of classical steroid hormone receptors in the mechanism of membrane action could be excluded. Nongenomic steroid effects on the plasma membrane are assumed. As the structure and function of biomembranes are modulated by lipid-bilayer fluidity and membranes crucially participate in nearly all aspects of cell biology, it is concluded that direct interactions of MPA with membranes potentially play a role in the antitumor activity of the compound.
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