Biomedical subjects

I Martinsen

Publications and source records attributed to I Martinsen.

8 recordsLinked to original sources

PubMed2002

Separation of human lymphocytes from citrated blood by density gradient (NycoPrep) centrifugation: monocyte depletion depending upon activation of membrane potassium channels.

Routine one-step centrifugation procedures (Lymphoprep = LP, Percoll) commonly used for separation of blood cells split the cells into two major fractions. After centrifugation the mononuclear cells (MNC = monocytes and lymphocytes) are located on the top of the separation fluid, whereas erythrocytes and granulocytes have sedimented to the bottom. We now show that a relatively pure lymphocyte suspension can be obtained by one-step centrifugation of citrated blood by using NycoPrep (NP = iohexol), a nonionic X-ray contrast agent. With this gradient medium also the monocytes pass to the bottom, leaving lymphocytes on the top. In parallel separations with LP, which contains Ficoll and a fully dissociated sodium salt of a contrast medium, the results were as usual, i.e. approximately 70-85% lymphocytes and 30-15% monocytes in the top fraction. The monocyte depletion with NP depended upon the use of citrated (ACD) blood and a proper balance of density and osmolality of the gradient medium, and was enhanced by 20 min preincubation with CaCl2 at room temperature. Monocyte depletion could not be obtained with LP. Under optimal conditions (density 1.075 g/ml, osmolality 280-300 mOsm/kg), the monocyte admixture amounted to approximately 1 (0-2)%, in separations with buffy coat samples. For freshly drawn blood, it was necessary to slightly modify the NP solution. The monocyte depletion was counteracted by blockers of K+ channels or by KCl in the cell suspension. Following incubation in NP of Percoll-separated cells, an enhanced release of K+ was observed. The results are interpreted as follows: NP mediates the opening of K+ channels of MNC, which leads to efflux of K+, accompanied with associated anions (Cl-). This reduces the osmolality inside the cells which therefore expel water to maintain osmotic equilibrium. In this regard it appears that monocytes are more sensitive than lymphocytes, their density therefore increasing more, so that they are able to pass the density barrier otherwise exerted by the gradient medium.

Blood Platelets↗

PubMed2000

Quantification of gadodiamide as Gd in serum, peritoneal dialysate and faeces by inductively coupled plasma atomic emission spectroscopy and comparative analysis by high-performance liquid chromatography.

An inductively coupled plasma atomic emission spectroscopy (ICP-AES) method for determination of gadodiamide as Gd in serum, peritoneal dialysate and faeces was developed. The within-day and between-day precision for determination of Gd in serum and peritoneal dialysate were 0.60-2.9 and 1.8-4.4%, respectively, and the accuracy was 98.0-99.3%. The quantification limits in serum and peritoneal dialysate were 6.5 and 1.6 microM Gd, respectively. The within-day and between-day precision determination of gadolinium in faeces were 1.0-5.3 and 2.2-7.9%, respectively, and the accuracy was 104-116%. The quantification limit was 11 nmol Gd/g dry weight. For the high-performance liquid chromatography (HPLC) method, the within-day precision in determination of gadodiamide in peritoneal dialysate was 1.2% and the accuracy was 103%. The quantification limit was 0.9 microM Gd. Comparative analysis of gadodiamide in serum and peritoneal dialysate from severely impaired renal patients by ICP-AES and HPLC revealed no metabolism of chelator or transmetallation of gadolinium, even in samples obtained as long as 7 days after dosing. Furthermore, the ICP-AES determination of Gd in faeces allows for the determination of faeces content of Gd corresponding to less than 0.1% of a clinical dosage of a Gd-based contrast medium.

Chromatography, High Pressure Liquid↗

PubMed1997

MR imaging properties and pharmacokinetics of MnDPDP in healthy volunteers.

PURPOSE: Thirteen male volunteers were studied to evaluate the MR imaging properties and pharmacokinetics of 10 mM mangafodipir trisodium infusion (MnDPDP, Teslascan). MATERIAL AND METHODS: Doses of 5 and 10 mumol/kg b.w. were administered by bolus injection (< 1 min) to 5 subjects, and by infusion (20 min) to 8 subjects, with a 3-week wash-out between doses. Infusion subjects underwent MR imaging. RESULTS: At 1 h after infusion, the plasma concentration of Mn was reduced to approximately 15% of the maximum value. Fifteen to 20% of Mn was recovered in the urine, and 50-60% was recovered in the faeces. The rapid initial plasma clearance of Mn is consistent with both rapid tissue uptake and rapid renal elimination. Increases in signal intensity were apparent on T1-weighted images of the liver, pancreas, spleen, renal cortex and the renal medulla, but not in regions of the brain protected by an intact blood-brain barrier. Increases were seen in the choroid plexus and pituitary. Contrast-related adverse events, only flushing of moderate intensity, occurred in bolus injection subjects. CONCLUSION: At 5 and 10 mumol/kg, mangafodipir produces relatively long-lasting enhancement of several abdominal organs, including the liver, pancreas and kidney.

Adult↗

PubMed1997

Metabolism and pharmacokinetics of MnDPDP in man.

PURPOSE: To study the metabolism and pharmacokinetics of mangafodipir trisodium injection, 0.01 mmol/ml (Teslascan), in healthy male volunteers. MATERIAL AND METHODS: Eight volunteers received mangafodipir trisodium as an infusion over 20 min, and 5 received it as an injection (< 1 min). Both groups received 5 and 10 mumol/kg b.w. with a wash-out period of 3 weeks between doses. Metabolites were measured in plasma, total manganese and zinc were measured in plasma and urine and total manganese was measured in faeces. RESULTS: The parent compound MnDPDP (manganese dipyridoxyl diphosphate) and 5 metabolites; MnDPMP (manganese dipyridoxyl monophosphate). MnPLED (manganese dipyridoxyl ethylenediamine) and the corresponding zinc compounds ZnDPDP, ZnDPMP and ZnPLED, were detected in plasma. ZnPLED was the only detectable metabolite 8 h after dosing. The apparent volume of distribution of manganese exceeded the interstitial body fluids. The volume of distribution of the ligand indicated distribution to the extracellular fluid only, with the plasma clearance close to the glomerular filtration rate. The manganese was incompletely excreted during the 4 days after treatment with the major part in faeces and less than 20% of the dose in the urine. CONCLUSION: Dephosphorylation and simultaneous transmetallation with zinc are the main metabolic pathways of MnDPDP in man.

Chromatography, High Pressure Liquid↗

PubMed1997

NMR relaxation studies with MnDPDP.

PURPOSE: Our studies were designed to compare the efficacy of mangafodipir trisodium (MnDPDP, Teslascan) as a tissue-specific MR agent with that of manganese chloride (MnCl2), to compare the efficacy of different doses and rates of administration of MnDPDP, and to collect the data needed for predicting optimum pulse sequences. MATERIAL AND METHODS: The dose response for the relaxation rates R1 and R2 at 0.47 T, and the manganese (Mn) concentrations in rat liver and in the liver, pancreas, heart and adrenals of pigs was determined for both MnDPDP and MnCl2 administered i.v. Computer simulations were carried out to model the effects of different tissue Mn concentrations and TR on signal intensities and contrast-to-noise ratios. RESULTS: In rat liver and pig organs both compounds produced a positive dose-response in R1 and tissue Mn concentration, and only small or no response in R2. The Mn concentration in rat liver was positively correlated with R1, regardless of the form in which Mn was given, or the rate of administration. Optimal imaging parameters are therefore expected to be different pre- and post-MnDPDP administration. CONCLUSION: The added cardiovascular safety of MnDPDP compared with MnCl2 does not result in loss of efficacy in increasing RI at the intended clinical dose of 5 mumol/kg MnDPDP. The changes in R2 were too small to affect T2-weighted images. The data give the basis for choosing the appropriate pulse sequences for MnDPDP-enhanced MR imaging.

Animals↗

PubMed1997

Tissue distribution and general safety of MnDPDP in male beagle dogs, with or without total common bile duct obstruction.

PURPOSE: Evaluation of the tissue distribution of manganese (Mn) and general safety in normal and cholestatic male beagle dogs after i.v. administration of mangafodipir trisodium (MnDPDP, Teslascan). MATERIAL AND METHODS: Male beagle dogs, with or without surgical obstruction of the common bile duct, received a single i.v. bolus injection of saline (control), or MnDPDP at doses of 10 or 50 mumol/kg b.w. and were sacrificed 1 or 7 days after treatment. Toxicity was assessed and tissue concentrations of Mn were measured. RESULTS: Increased tissue Mn concentrations were found in all dogs treated with MnDPDP and were greatest in those with biliary obstruction. Although Mn concentrations decreased with time in most tissues in each of the treated groups, this was not the case for the brain and adrenal glands in dogs with total biliary obstruction in which further increases in Mn concentrations were seen at the later time point. This suggested a re-distribution of Mn from the major body depots such as the liver. There were no effects of MnDPDP on clinical signs/behaviour, organ weights, histomorphology or clinical biochemistry. CONCLUSION: These findings indicate that a single clinical dose of 5 mumol/kg MnDPDP is likely to be well tolerated in patients with cholestasis.

Animals↗

PubMed1986

Multielemental characterization of human lung tissues by ICP-AES.

Preliminary results on multielement analysis of human lung tissues with inductively coupled plasma atomic emission spectrometry (ICP-AES) are reported. Three different sample preparation procedures have been studied; dry ashing at 450 degrees C or low temperature ashing followed by pressure digestion with aqua regia and hydrofluoric acid or direct acid digestion with nitric-, sulfuric- and perchloric acid.

Elements↗

PubMedDate not supplied

Effects of low mercury vapour exposure on the thyroid function in chloralkali workers.

Forty-seven chloralkali workers exposed to mercury vapour for an average of 13.3 years were compared with 47 referents matched for age in a cross-sectional study of thyroid function. The mean urinary mercury concentration in the exposed workers was low compared with other studies of chloralkali workers: 5.9 nmol mmol-1 creatinine (range 1.1-16.8) vs 1.3 nmol mmol-1 creatinine (range 0.2-5.0) in the reference group. The median serum concentration of reverse triiodothyronine (rT3) was statistically significantly higher in the exposed subjects compared with the referents (268 pmol l (-1) and range 161-422 vs 240 pmol l(-1) and range 129-352; P = 0.009). The difference between the exposed subjects and the referents was most pronounced in the highest exposed sub-groups. The free thyroxine (T4)/free T3 ratio was also higher in the highest exposed subgroups compared with the referents. The median serum concentration of tumour necrosis factor alpha (TNF-alpha) was lower in the exposed subjects (7.3 pg ml(-1) and range 4.4-69.7 vs 8.0 pg ml(-1) and range 6.0-34.6; P = 0.004). Exposed subjects with the lowest urinary iodine (<67.8 nmol mmol(-1) Cr) had higher serum concentrations of reverse T 3 and a higher free T4/free T3 ratio than the other subjects, suggesting that a low concentration of iodine in urine may be a risk factor for increased serum concentrations of reverse T3 and the free T4/free T3 ratio in subjects exposed occupationally to mercury vapour. The study could indicate a slight effect of low mercury vapour exposure on the function of the enzyme type I iodothyronine deiodinase, possibly modified by comparatively low urinary iodine concentrations.

Adult↗