Steroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias caused by matrix effects, thus assessing potential matrix effects is an important step in combining circulating tumour DNA (ctDNA) analysis with hormone status.We investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain ctDNA, compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in samples obtained from ten healthy controls and ten castration-resistant prostate cancer (CRPC) patients.Steroid measurements were comparable between MSP and serum. A small but consistent decrease of 8–21% compared to serum was observed when using CS plasma, which was considered to be within the acceptable margin. The minimal residual testosterone levels of CRPC patients could be sensitively quantified in both MSP and CS samples.We validated the use of MSP and CS samples for multi-steroid profiling by LC–MS/MS. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients.
This book tells the story behind the development of some industrial processes based on a variety of organic …
Serum concentrations of Apolipoprotein A-I and A-II, (Apo A-1 and Apo A-II) HDL-cholesterol (HDL-C), Total Cholesterol (TC), triglycerides (TG) and lipoprotein electrophoresis were assayed serially in the second half of normal pregnancy (21 women), in pre-eclampsia (26 women) and in both groups one and six weeks after delivery. In the normal group we found increased concentrations of Apo A-I and HDL-C, which remained unaltered during pregnancy. Apo A-II was unchanged. Correlation coefficients for Apo A-II vs HDL-C and Apo A-I vs Apo A-II decreased gradually towards delivery while it remained at an elevated and unaltered level for Apo A-I vs HDL-C. The Apo A-I/HDL-C ratio was unaltered during the whole study while the Apo A-I/A-II ratio was elevated during pregnancy and the Apo A-II/HDL-C ratio was reduced. These results may indicate a gradual change in the surface structure of the HDL particle or its subfractions. In pre-eclampsia Apo A-I and HDL-C concentrations were reduced, TG was increased and Apo A-II and TC were unchanged when compared with the normal pregnancy group. A more pronounced correlation coefficient was recorded for Apo A-I vs HDL-C than for Apo A-II vs HDL-C and Apo A-I vs Apo II. The results indicate that from an atherogenic point of view normal pregnancy seems more beneficial than pre-eclampsia.
Changes in renal hemodynamics, sodium homeostasis, renal acidifying capacity, and aldosterone excretion were studied before and after long-term intravenous essential fatty acid supplementation for a period of 3 years in 11 patients with cystic fibrosis. The mean (+/- SD) glomerular filtration rate was high at the start of the study (133 +/- 18 ml/min/1.73 m2 body surface area) and decreased significantly (p less than 0.05) to within normal values after 1 year of essential fatty acid supplementation. The urinary elimination of an oral sodium load initially was very low (3.6 +/- 2.5 mmol/hr/1.73 m2 body surface area vs control subjects' values of 7.9 +/- 2.0; p less than 0.001) and increased during treatment but was not normalized (p less than 0.05 vs control subjects' values). Free water clearance and distal tubular sodium delivery, which were significantly decreased before treatment (p less than 0.01 and p less than 0.001 vs control subjects' values, respectively) did not increase significantly. The mean urinary aldosterone excretion did not significantly differ from that in control subjects before and after treatment. The acidifying capacity was disturbed, indicating a low renal bicarbonate threshold, and was changed during treatment in only 2 of 10 patients. These data indicate that essential fatty acid deficiency may contribute to the renal disturbances in cystic fibrosis.
The main diagnostic criteria in cystic fibrosis (CF) is an elevated concentration of sodium chloride in sweat. As the kidney is the main regulator of sodium homeostasis it was of special interest to study renal function in CF. Sixteen patients with CF, 5-19 years of age, were studied. Oral and intravenous (iv) sodium load tests were performed including clearances of inulin and PAH. Standardized clearance technique was used. Glomerular filtration rate (GFR) and filtration fraction (FF) were increased compared to controls. Renal plasma flow was normal. Basal urinary sodium excretion as well as renal responses to oral and iv sodium loads were low indicating an increased renal sodium reabsorption. Diluting capacity was decreased because of a low distal sodium delivery indicating an increased proximal sodium reabsorption. Ten CF-children were treated with IntralipidR at regular intervals for one year. The GFR decreased to normal values and the urinary elimination rate of an oral sodium load was still low but increased significantly compared to that before treatment. The increased GFR and proximal sodium reabsorption found in CF might be due to a change in fatty acid composition of the cell membrane and/or a disturbance of the prostaglandin metabolism.