Vitamin D deficiency is present in a majority of haemodialysis patients. Supplementation with cholecalciferol is safe, well tolerated and reasonable to replenish vitamin D stores in haemodialysis patients. However, only 57% of patients achieved recommended calcidiol levels, thus favouring additional dose-finding studies.

The first analytical method for simultaneous speciation analysis of five of the most important gadolinium-based magnetic resonance imaging (MRI) contrast agents in blood plasma samples was developed. Gd-DTPA (Magnevist), Gd-BT-DO3A (Gadovist), Gd-DOTA (Dotarem), Gd-DTPA-BMA (Omniscan), and Gd-BOPTA (Multihance) were separated by hydrophilic interaction liquid chromatography (HILIC) and detected with electrospray mass spectrometry (ESI-MS). Spiking experiments of blank plasma with Magnevist and Gadovist were performed to determine the analytical figures of merit and the recovery rates. The limits of detection ranged from 1 x 10 (-7) to 1 x 10 (-6) mol/L depending on the ionization properties of the individual compounds, and limits of quantification ranged from 5 x 10 (-7) to 5 x 10 (-6) mol/L. The linear concentration range comprised 2 orders of magnitude. With application of this method, blood plasma samples of 10 healthy volunteers, with Magnevist or Gadovist medication, were analyzed for Gd-DTPA and Gd-BT-DO3A, respectively. The obtained results were successfully validated with inductively coupled plasma-optical emission spectroscopy (ICP-OES).

To study transmetalation effects of the gadolinium-based contrast agent Magnevist (Gd-DTPA), the first analytical method for the simultaneous determination of Gd-DTPA and its transmetalation products in complex clinical samples was developed. The high separation efficiency of capillary electrophoresis (CE) was employed to separate Gd-DTPA, Fe-DTPA, Cu-DTPA, Zn-DTPA, and the free DTPA (diethylenetriaminepentaacetic acid) ligand. The coupling of CE with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) provided the required sensitivity and excellent selectivity for the analysis of complex samples, such as blood plasma and whole blood. Separation and detection parameters were optimized, and crucial steps for CE/MS method development are pointed out. Limit of detection (LOD) is 5 x 10(-7) mol/L, limit of quantification (LOQ) is 1.7 x 10(-6) mol/L, and the linear range comprises 2 decades, starting at the limit of quantification. To determine recovery rates, precision, and accuracy of the method, blank plasma samples were spiked with Gd-DTPA in three different concentrations. Blood plasma samples from 10 patients with normal renal function, having received Magnevist, were analyzed for Gd-DTPA and possible transmetalation products by CE/ESI-TOF-MS. The method was validated by determination of the total Gd concentration using inductively coupled plasma optical emission spectroscopy (ICP-OES). Transmetalation assays of Magnevist with and without supplementary iron were carried out in incubated whole blood samples.

A novel method for the analysis of Gadolinium-based contrast agents in complex clinical matrices is presented. Three commonly applied ionic contrast agents for magnetic resonance imaging were separated by CE and detected by ESI-MS. Blank urine samples were spiked with Dotarem (Gd-DOTA, Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), Magnevist (Gd-DTPA, Gadolinium-diethylenetriaminepentaacetic acid) and Multihance (Gd-BOPTA, Gadolinium-benzyloxymethyl-diethylenetriaminepentaacetic acid) to determine the recovery rates. The figures of merit were determined with LODs as low as 2.0 x 10(-7) mol/L for Gd-DOTA, 5.0 x 10(-7) mol/L for Gd-DTPA and 1.0 x 10(-6) mol/L for Gd-BOPTA. The respective LOQs were 6.6 x 10(-7) mol/L for Gd-DOTA, 1.5 x 10(-6) mol/L for Gd-DTPA and 3.3 x 10(-6) mol/L for Gd-BOPTA. The linear working range comprised two orders of magnitude starting at the LOQ, with regression coefficients of R > or = 0.999 for all investigated analytes. Using this CE-MS method, Gd-DOTA was quantified in seven urine samples obtained at different times after delivery from a volunteer magnetic resonance imaging patient who was treated with Dotarem. Additionally, total Gd concentrations were determined by means of ICP-optical emission spectroscopy to validate the CE-MS data. To compensate for dietary dilution effects of the urine samples, creatinine was determined by HPLC with UV/Vis absorption detection. Gd-DOTA concentrations were normalized to urinary creatinine, illustrating the fast excretion kinetics of Gd-DOTA.

The withdrawal of cyclosporine in renal transplant patients, receiving relatively low doses of cyclosporine, resulted in a substantial decrease in blood pressure. However, MSNA and norepinephrine did not change. This suggests that cyclosporine treatment does not cause chronic sympathetic activation that could explain the cyclosporine-induced blood pressure elevation in renal transplant patients.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium-binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels, and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives our group showed increased calcium and a decreased magnesium and increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4 +/- 9.8 mm Hg) and 13 normotensive rats (NT, systolic blood pressure 118.5 +/- 7.2 mm Hg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick; the calcium content was 124.7 +/- 4.5 mmol/kg dry weight in SHR versus 110.3 +/- 4.1 mmol/kg dry weight in NT (mean +/- SD, P <.01 for both), the magnesium content was 35.5 +/- 3.9 in SHR versus 50.1 +/- 4.9 mmol/kg dry weight in NT (P <.01 for both). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56 +/- 3.9 versus 2.23 +/- 0.27 [P <.01 for both]). Thus, aortic smooth muscle cells from SHR are characterized by a markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. Cellular calcium and magnesium handling is disturbed in SHR aortic smooth muscle cells as it is in hypertensive blood cells. The increased calcium/magnesium ratio in hypertensive cells is a pathogenetic factor for the development of arteriosclerosis and hypertension.

In ESRD patients, low-dose MOX produced sustained and substantial reductions in sympathetic outflow without hemodynamically compromising them. We suggest that the inhibition of central sympathetic outflow may improve cardiovascular prognosis in ESRD.

Intracellular Mg2؉ measurements were performed in erythrocyte membranes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg 2؉ concentrations were determined by atomic absorption spectroscopy using a Video 12 apparatus. The results show that in patients with essential hypertension total Mg 2؉ content in erythrocyte membranes was significantly decreased as compared with the control group (0.28 ؎ ؎ 0.05 v 0.52 ؎ ؎ 0.15 mmol/g membrane protein; mean ؎ ؎ SD, P < < .001). Additionally, plasma and free intracellular Mg 2؉ content of lymphocytes and