Erik Sprengers - Academia.edu (original) (raw)
Papers by Erik Sprengers
Journal of Membrane Science, 1992
The effect of two commonly used sterlhzatlon methods for artificial kidneys on the morphology and... more The effect of two commonly used sterlhzatlon methods for artificial kidneys on the morphology and performance of hollow fiber Hemophan@ hemodlalysls membranes was studied A relatively new membrane characterlzatlon method, thermoporometry, was used to determine the pore size dlstrlbutlons and porosltles of the differently treated membrane samples The samples used for this study were not treated with a concentrated glycerol solution before sterlhzatlon Hemophan was found to have a pore size dlstrlbutlon with pore radn between 1 5 and 12 nm, the volume porosity was 20% The sample sterilized with ethylene oxide (EtO) had a volume porosity of 18% which was due to a decrease of the pore volume of the smallest pores The applied dry steam stenhzatlon treatment resulted m a drastic collapse of the large pores while smaller pores were formed The calculated porosity was only 10% The 'tortuous capillary pore model' was used to predict the performance of the artificial kidneys from the pore size dlstrlbutlon m the membrane material In ultra dialysis experiments with creatmme and vitamin Bl2 were carried out to compare the calculated and measured clearance rates Also the ultrafiltration capacity of the devices was determined It was found that a reasonable estimation of the ultraflltratlon capacity could be made The calculated clearance rates were systematically underestimated, although the relative dependence of the clearance rates on the applied sterlhzatlon methods was approximated reasonably Keywords artificial kidney, dlalysls, including Donnan, membrane preparation and structure, membrane charactenzatlon, thermoporometry A P Broek et al/J Membrane Scl 73 (1992) [143][144][145][146][147][148][149][150][151][152]
Journal of Membrane Science, 1995
Inverse size exclusion chromatography (i-SEC) was used to characterize three different cellulosic... more Inverse size exclusion chromatography (i-SEC) was used to characterize three different cellulosic hollow fiber hemodialysis membranes, i.e. low-flux cuprophan and hemophan and high-flux RC-HP400A. With the i-SEC technique the pore size distribution and porosity of a membrane can be determined and adsorption phenomena can be studied. The membranes showed clear differences in pore size and porosity, the high-flux RC-HP400A membrane has a larger pore size as well as a higher porosity. For all the membranes it was found that the elution curves were best described by a homoporous pore volume distribution. It appeared that the bound or non-freezing water in the membranes was at least partly accessible to solutes. The test molecules creatinine and vitamin B12 both adsorbed to the cellulosic membranes. The adsorption behavior of creatinine was strongly dependent on the NaCI concentration present. The observations could be explained by assuming that cuprophan and RC-HP400A are negatively charged whereas hemophan is positively charged due to the modification with N,N-diethylaminoethyl ether. The net charge of the hemophan is smaller.
Clinica Chimica Acta, 1979
1. Maleic acid is shown to be able to bind the thiol compound 2-mercaptoethanol. This is fully co... more 1. Maleic acid is shown to be able to bind the thiol compound 2-mercaptoethanol. This is fully consistent with the data of Morgan and Friedman (1938). 2. Human erythrocyte pyruvate kinase dissolved and quantitated in Tris-maleate shows a loss of positive homotropic interactions, as compared to the same preparation in Tris-HCl. Hill coefficients (n) of n = 1.0-1.2 and n = 1.6-1.8 are obtained in Tris-maleate and Tris-HCl respectively. Half saturation [S] 0.5 and Vmax remain unchanged. Pyruvate kinase in Tris-maleate is slightly more stable to heating at 60 degrees C than in Tris-HCl. Incubation of the enzyme in Tris-maleate for one h with high concentrations of dithiotreitol restores the positive homotropic interactions. 3. It is proposed, that the abnormalities of the pyruvate kinase of some patients with acquired pyruvate kinase deficiency, obtained from a study in Tris-maleate, may partly be induced by the buffer itself.
Biochimica et Biophysica Acta (BBA) - General Subjects, 1983
Rat brain mitochondrial hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was solubiliz... more Rat brain mitochondrial hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was solubilized by treatment of the mitochondria with glucose 6-phosphate and partly purified. The solubilized enzyme was compared with the cytosolic enzyme fraction. The solubilized and cytosolic enzymes were also compared with the enzyme bound to the mitochondrial membrane. The following observations were made. 1. There is no difference in electrophoretic mobility on cellulose-acetate between the cytosolic and the solubilized enzyme. Both fractions are hexokinase isoenzyme I. 2. There is no difference in kinetic parameters between the cytosolic or solubilized enzymes (P less than 0.001). For the cytosolic enzyme Km for glucose was 0.067 mM (S.E. = 0.024, n = 7); Km for MgATP2- was 0.42 mM (S.E. = 0.13, n = 7) and Ki,app for glucose 1,6-diphosphate was 0.084 mM (S.E. = 0.011, n = 5). For the solubilized enzyme Km for glucose was 0.071 mM (S.E. = 0.021, n = 6); Km for MgATP2- was 0.38 mM (S.E. = 0.11, n = 6) and Ki,app for glucose 1,6-diphosphate was 0.074 mM (S.E. = 0.010, n = 5). However when bound to the mitochondrial membrane, the enzyme has higher affinities for its substrates and a lower affinity for the inhibitor glucose 1,6-diphosphate. For the mitochondrial fraction Km for glucose was 0.045 mM (S.E. = 0.013, n = 7); Km for MgATP2- was 0.13 mM (S.E. = 0.02, n = 7) and Ki,app for glucose 1,6-diphosphate was 0.33 mM (S.E. = 0.03, n = 5). 3. The cytosolic and solubilized enzyme could be (re)-bound to depleted mitochondria to the same extent and with the same affinity. Limited proteolysis fully destroyed the enzyme's ability to bind to depleted mitochondria. 4. Our data support the hypothesis that soluble- and solubilizable enzyme from rat brain are one and the same enzyme, and that there is a simple equilibrium between the enzyme in these two pools.
Drug Discovery Today, 2010
The pharmaceutical industry must find ways to improve the unacceptably high attrition rate during... more The pharmaceutical industry must find ways to improve the unacceptably high attrition rate during drug development. Clearly, pharma has moved away from treat-and-see testing of new drugs in patients, with a strong current focus on generating translational biomarkers early in the research process to enable more predictive evaluation of drug action in clinical trials. Underlying such a translational medicine approach is the intensive search for and use of high-quality biomarkers indicative of successful drug target engagement, pharmacological effects, efficacy or safety. This review outlines our rational question-based drug development strategy in which biomarker data drive decisions on which drug candidates to progress to clinical testing.
Journal of Membrane Science, 1992
The effect of two commonly used sterlhzatlon methods for artificial kidneys on the morphology and... more The effect of two commonly used sterlhzatlon methods for artificial kidneys on the morphology and performance of hollow fiber Hemophan@ hemodlalysls membranes was studied A relatively new membrane characterlzatlon method, thermoporometry, was used to determine the pore size dlstrlbutlons and porosltles of the differently treated membrane samples The samples used for this study were not treated with a concentrated glycerol solution before sterlhzatlon Hemophan was found to have a pore size dlstrlbutlon with pore radn between 1 5 and 12 nm, the volume porosity was 20% The sample sterilized with ethylene oxide (EtO) had a volume porosity of 18% which was due to a decrease of the pore volume of the smallest pores The applied dry steam stenhzatlon treatment resulted m a drastic collapse of the large pores while smaller pores were formed The calculated porosity was only 10% The 'tortuous capillary pore model' was used to predict the performance of the artificial kidneys from the pore size dlstrlbutlon m the membrane material In ultra dialysis experiments with creatmme and vitamin Bl2 were carried out to compare the calculated and measured clearance rates Also the ultrafiltration capacity of the devices was determined It was found that a reasonable estimation of the ultraflltratlon capacity could be made The calculated clearance rates were systematically underestimated, although the relative dependence of the clearance rates on the applied sterlhzatlon methods was approximated reasonably Keywords artificial kidney, dlalysls, including Donnan, membrane preparation and structure, membrane charactenzatlon, thermoporometry A P Broek et al/J Membrane Scl 73 (1992) [143][144][145][146][147][148][149][150][151][152]
Journal of Membrane Science, 1995
Inverse size exclusion chromatography (i-SEC) was used to characterize three different cellulosic... more Inverse size exclusion chromatography (i-SEC) was used to characterize three different cellulosic hollow fiber hemodialysis membranes, i.e. low-flux cuprophan and hemophan and high-flux RC-HP400A. With the i-SEC technique the pore size distribution and porosity of a membrane can be determined and adsorption phenomena can be studied. The membranes showed clear differences in pore size and porosity, the high-flux RC-HP400A membrane has a larger pore size as well as a higher porosity. For all the membranes it was found that the elution curves were best described by a homoporous pore volume distribution. It appeared that the bound or non-freezing water in the membranes was at least partly accessible to solutes. The test molecules creatinine and vitamin B12 both adsorbed to the cellulosic membranes. The adsorption behavior of creatinine was strongly dependent on the NaCI concentration present. The observations could be explained by assuming that cuprophan and RC-HP400A are negatively charged whereas hemophan is positively charged due to the modification with N,N-diethylaminoethyl ether. The net charge of the hemophan is smaller.
Clinica Chimica Acta, 1979
1. Maleic acid is shown to be able to bind the thiol compound 2-mercaptoethanol. This is fully co... more 1. Maleic acid is shown to be able to bind the thiol compound 2-mercaptoethanol. This is fully consistent with the data of Morgan and Friedman (1938). 2. Human erythrocyte pyruvate kinase dissolved and quantitated in Tris-maleate shows a loss of positive homotropic interactions, as compared to the same preparation in Tris-HCl. Hill coefficients (n) of n = 1.0-1.2 and n = 1.6-1.8 are obtained in Tris-maleate and Tris-HCl respectively. Half saturation [S] 0.5 and Vmax remain unchanged. Pyruvate kinase in Tris-maleate is slightly more stable to heating at 60 degrees C than in Tris-HCl. Incubation of the enzyme in Tris-maleate for one h with high concentrations of dithiotreitol restores the positive homotropic interactions. 3. It is proposed, that the abnormalities of the pyruvate kinase of some patients with acquired pyruvate kinase deficiency, obtained from a study in Tris-maleate, may partly be induced by the buffer itself.
Biochimica et Biophysica Acta (BBA) - General Subjects, 1983
Rat brain mitochondrial hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was solubiliz... more Rat brain mitochondrial hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was solubilized by treatment of the mitochondria with glucose 6-phosphate and partly purified. The solubilized enzyme was compared with the cytosolic enzyme fraction. The solubilized and cytosolic enzymes were also compared with the enzyme bound to the mitochondrial membrane. The following observations were made. 1. There is no difference in electrophoretic mobility on cellulose-acetate between the cytosolic and the solubilized enzyme. Both fractions are hexokinase isoenzyme I. 2. There is no difference in kinetic parameters between the cytosolic or solubilized enzymes (P less than 0.001). For the cytosolic enzyme Km for glucose was 0.067 mM (S.E. = 0.024, n = 7); Km for MgATP2- was 0.42 mM (S.E. = 0.13, n = 7) and Ki,app for glucose 1,6-diphosphate was 0.084 mM (S.E. = 0.011, n = 5). For the solubilized enzyme Km for glucose was 0.071 mM (S.E. = 0.021, n = 6); Km for MgATP2- was 0.38 mM (S.E. = 0.11, n = 6) and Ki,app for glucose 1,6-diphosphate was 0.074 mM (S.E. = 0.010, n = 5). However when bound to the mitochondrial membrane, the enzyme has higher affinities for its substrates and a lower affinity for the inhibitor glucose 1,6-diphosphate. For the mitochondrial fraction Km for glucose was 0.045 mM (S.E. = 0.013, n = 7); Km for MgATP2- was 0.13 mM (S.E. = 0.02, n = 7) and Ki,app for glucose 1,6-diphosphate was 0.33 mM (S.E. = 0.03, n = 5). 3. The cytosolic and solubilized enzyme could be (re)-bound to depleted mitochondria to the same extent and with the same affinity. Limited proteolysis fully destroyed the enzyme's ability to bind to depleted mitochondria. 4. Our data support the hypothesis that soluble- and solubilizable enzyme from rat brain are one and the same enzyme, and that there is a simple equilibrium between the enzyme in these two pools.
Drug Discovery Today, 2010
The pharmaceutical industry must find ways to improve the unacceptably high attrition rate during... more The pharmaceutical industry must find ways to improve the unacceptably high attrition rate during drug development. Clearly, pharma has moved away from treat-and-see testing of new drugs in patients, with a strong current focus on generating translational biomarkers early in the research process to enable more predictive evaluation of drug action in clinical trials. Underlying such a translational medicine approach is the intensive search for and use of high-quality biomarkers indicative of successful drug target engagement, pharmacological effects, efficacy or safety. This review outlines our rational question-based drug development strategy in which biomarker data drive decisions on which drug candidates to progress to clinical testing.