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Borje Haraldsson - One of the best experts on this subject based on the ideXlab platform.

  • beneficial effects of Orosomucoid on the glomerular barrier in puromycin aminonucleoside induced nephrosis
    Nephrology Dialysis Transplantation, 2006
    Co-Authors: Clara Hjalmarsson, Martin E Lidell, Borje Haraldsson
    Abstract:

    Background. In a hitherto unconfirmed report, Orosomucoid was reported to ameliorate the nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats. Methods. We wanted to test this hypothesis and extend the analysis of the effects on the glomerular barrier. Glomerular filtration rate (GFR), and fractional clearance for albumin (θ albumin ) and for neutral Ficolls were estimated in cooled isolated perfused kidneys. Modern transport equations were used to estimate glomerular size selectivity and charge selectivity. Also, podocyte morphology was studied. Four groups of rats (4 x n = 8) were administered PAN intraperitoneally and treated daily for 5 days with Orosomucoid in two different doses (groups A and B), albumin (group C) or saline (group D). Two additional groups of rats (2 × n=8) were used as controls and these rats received either saline (group E) or Orosomucoid (group F) but no PAN. Results. Treatment with Orosomucoid restored podocyte morphology and renal function from the damaging effects of PAN in a dose-dependent manner. GFR was significantly reduced by PAN (groups C and D) when compared with controls (groups E and F). This effect was partly (group A) or completely (group B) reversed by Orosomucoid. The θ albumin was 0.002±0.001 (mean ± SEM) in controls (group E) and was unaffected by Orosomucoid per se (group F). PAN increased θ albumi n to 0.020±0.001 in group C and to 0.021±0.001 in group D, while it was significantly less in group A, 0.014±0.001, P<0.05. The heterogeneous charged fibre model analysis revealed that PAN reduced the relative volume of negatively charged fibres, Φ, from 7.1±0.08% (group E) to 48% of this value in groups C and D (P<0.001); Φ was 4.5±0.04% in group A, 5.3±0.44% in group B, and 6.1±0.11% in group F. Conclusion. High doses of Orosomucoid completely normalized the glomerular barrier in six out of eight animals with puromycin-induced nephrotic syndrome. Thus, Orosomucoid has a promising therapeutic potential for certain kidney disorders.

  • Beneficial effects of Orosomucoid on the glomerular barrier in puromycin aminonucleoside-induced nephrosis
    Nephrology Dialysis Transplantation, 2006
    Co-Authors: Clara Hjalmarsson, Martin E Lidell, Borje Haraldsson
    Abstract:

    Background. In a hitherto unconfirmed report, Orosomucoid was reported to ameliorate the nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats. Methods. We wanted to test this hypothesis and extend the analysis of the effects on the glomerular barrier. Glomerular filtration rate (GFR), and fractional clearance for albumin (θ albumin ) and for neutral Ficolls were estimated in cooled isolated perfused kidneys. Modern transport equations were used to estimate glomerular size selectivity and charge selectivity. Also, podocyte morphology was studied. Four groups of rats (4 x n = 8) were administered PAN intraperitoneally and treated daily for 5 days with Orosomucoid in two different doses (groups A and B), albumin (group C) or saline (group D). Two additional groups of rats (2 × n=8) were used as controls and these rats received either saline (group E) or Orosomucoid (group F) but no PAN. Results. Treatment with Orosomucoid restored podocyte morphology and renal function from the damaging effects of PAN in a dose-dependent manner. GFR was significantly reduced by PAN (groups C and D) when compared with controls (groups E and F). This effect was partly (group A) or completely (group B) reversed by Orosomucoid. The θ albumin was 0.002±0.001 (mean ± SEM) in controls (group E) and was unaffected by Orosomucoid per se (group F). PAN increased θ albumi n to 0.020±0.001 in group C and to 0.021±0.001 in group D, while it was significantly less in group A, 0.014±0.001, P

  • Orosomucoid has a camp dependent effect on human endothelial cells and inhibits the action of histamine
    American Journal of Physiology-heart and Circulatory Physiology, 2000
    Co-Authors: Jenny Sorensson, Maria Ohlson, Anna Bjornson, Borje Haraldsson
    Abstract:

    The plasma protein Orosomucoid (α1-acid glycoprotein) has previously been shown to constitute a critical component of the capillary barrier. The protein has also been suggested to act as an anti-in...

  • human endothelial cells produce Orosomucoid an important component of the capillary barrier
    American Journal of Physiology-heart and Circulatory Physiology, 1999
    Co-Authors: Jenny Sorensson, Borje Haraldsson, Goran Matejka, Maria Ohlson
    Abstract:

    The serum protein Orosomucoid (α1-acid glycoprotein) is needed to maintain the high capillary permselectivity required for normal homeostasis. It is not known how the protein executes its action, b...

J R Albani - One of the best experts on this subject based on the ideXlab platform.

  • new insights in the conformation of α1 acid glycoprotein Orosomucoid quenching resolved emission anisotropy studies
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1999
    Co-Authors: J R Albani
    Abstract:

    Abstract Quenching resolved emission anisotropy method was applied to study the dynamics of the two classes of Trp residues of human α1-acid glycoprotein (Orosomucoid), in the absence and presence of progesterone. In the absence of progesterone, the values of the anisotropies of the surface and buried Trp residues are 0.155 and 0.178, respectively. These values lower than the limiting anisotropy (0.267) indicate that both classes of Trp residues display residual motions. In the presence of progesterone, the values of the anisotropies decrease from 0.155 to 0.146 and from 0.178 to 0.167. Thus, binding of progesterone to Orosomucoid increases the internal dynamics of the protein. Also, the fact that in the absence or in the presence of progesterone, the anisotropies of both classes are close, means that the amplitudes of the motions of the two classes are not significantly different. From our data and from the well-known position of the carbohydrate residues on Orosomucoid, we suggest the presence of a hydrophobic pocket within the protein and where the ‘buried’ Trp residues can be found.

  • correlation between dynamics structure and spectral properties of human α1 acid glycoprotein Orosomucoid a fluorescence approach
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1998
    Co-Authors: J R Albani
    Abstract:

    Abstract Dynamics of proteins and membranes are usually investigated by red-edge excitation spectra and fluorescence anisotropy. In a viscous or rigid medium, the fluorescence maximum position changes with the excitation wavelength upon red-edge excitation. In addition to the shift in the emission maximum on red edge excitation, fluorescence anisotropy is also known to be dependent on the excitation and emission wavelengths in viscous media. However, this dependence has always been explained by the fact that the fluorophore is rigid, i.e. it does not diplay any residual motions. The aim of the present work was to check the validity of this latest assumption and to explain the possible origin of the dependence of the anisotropy on both the excitation and emission wavelengths. Therefore, we compared the results obtained from the fluorescence of the Trp residues of two α1-acid glycoproteins (Orosomucoid). One protein was purified by chromatographic methods (Orosomucoidc) and the other was obtained with ammonium sulfate precipitation (Orosomucoids). Trp residues of Orosomucoidc display free motions while those of Orosomucoids are rigid. The general qualitative feature of the excitation anisotropy spectra recorded on both types of preparation is identical and resembles that obtained for other proteins containing tryptophan residue in protein. The fluorescence anisotropy measured across the emission spectra decreases for both preparations, indicating that this phenomenon is characteristic for fluorophores surrounded by a rigid microenvironment or by a microenvironment that displays motions. The fluorescence anisotropy variation across the emission and the excitation spectra is more important when the fluorophore possesses constrained motions than when it displays a high degree of freedom. Our results clearly demonstrate that the tertiary structure of the protein and the structure and dynamics of the microenvironments of the Trp residues are the origin of the dependence of anisotropy on the excitation and emission wavelengths.

Merete Skovdal Christiansen - One of the best experts on this subject based on the ideXlab platform.

  • increased urinary Orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes
    Journal of Diabetes and Its Complications, 2010
    Co-Authors: Merete Skovdal Christiansen, E Hommel, Erik Magid, Lars Friberg, Jens Molvig, Bo Feldtrasmussen
    Abstract:

    Abstract Objectives Increased urinary Orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients with type 2 diabetes and normal or increased UOER. Methods We performed a cross-sectional study of 40 patients with type 2 diabetes (normal UOER, n =16; increased UOER, n =24) who displayed no signs of cardiovascular disease and 21 healthy control persons. The renal clearance values of [ 51 Cr]ethylenediaminetetraacetic acid ([ 51 Cr]EDTA), lithium, Orosomucoid, albumin, and sodium were measured. Results Patients with type 2 diabetes had normal glomerular filtration rate (GFR) measured by [ 51 Cr]EDTA clearance. The clearance value of Orosomucoid was highly increased in patients with increased UOER. The clearance values of albumin were similar in patients with increased UOER and in healthy controls. Investigations of renal tubular function revealed normal and similar levels of lithium clearance and proximal and distal reabsorption of sodium and water. Serum values of Orosomucoid were higher in patients with increased UOER than in healthy controls ( P P Conclusions Patients with type 2 diabetes and increased UOER had normal GFR and showed no signs of renal glomerular or tubular dysfunction. We therefore hypothesize that increased levels of UOER may be caused by local renal production of Orosomucoid due to chronic low-grade inflammation.

  • monitoring urinary Orosomucoid in acute inflammation observations on urinary excretion of Orosomucoid albumin α1 microglobulin and igg
    Clinical Chemistry, 2005
    Co-Authors: Erik Magid, Henrik Guldager, Dan Hesse, Merete Skovdal Christiansen
    Abstract:

    Background: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of Orosomucoid (α1-acid glycoprotein), albumin, α1-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. Methods: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. Results: During surgery-induced inflammation, the increase and decrease in Orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for Orosomucoid, 98-fold for α1-microglobulin, 33-fold for albumin, and 26-fold for IgG. Conclusions: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of Orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.

  • Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow up
    Diabetologia, 2005
    Co-Authors: Merete Skovdal Christiansen, E Hommel, Erik Magid, Bo Feldtrasmussen
    Abstract:

    Aims/hypothesis To study whether urinary Orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between Orosomucoid in serum and urine.

  • a particle enhanced turbidimetric immunoassay for quantitative determination of Orosomucoid in urine development validation and reference values
    Clinical Chemistry and Laboratory Medicine, 2004
    Co-Authors: Merete Skovdal Christiansen, Soren Blirupjensen, Lise Foged, Marianne Larsen, Erik Magid
    Abstract:

    Increased urinary Orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes, as demonstrated by a conventional, immunoturbidimetric method. We wanted to optimize the method by developing a fully automated, particle-enhanced turbidimetric (PET) immunoassay with a lower detection limit, to allow assessment of Orosomucoid in urine in healthy individuals and patients. A micro-particle-based immunoreagent was prepared for a PET immunoassay. The calibration was traceable to the certified reference material (CRM 470) for specific human serum proteins. We studied 69 healthy adults (28 men and 41 women) to establish reference values for the new assay. The detection limit of Orosomucoid in urine was found to be 0.05 mg/l, about 20 times lower than for the conventional assay. Within-run imprecision [CV%, (level)] was 6.7% (0.23 mg/l), 1.0% (1.08 mg/l) and 1.0% (4.69 mg/l). Total imprecision [CV%, (level)] was 10.4% (0.23 mg/l), 3.9% (1.08 mg/l) and 3.4% (4.69 mg/l). Reference values [median (2.5-97.5 percentiles)] for UOER were 0.36 (0.07-2.04) μg/min and for urinary Orosomucoid/creatinine ratio 0.04 (0.009-0.17) mg/mmol. We describe a fully automated, transferable, sufficiently precise, high-sensitivity assay for Orosomucoid in urine and present reference values traceable to CRM 470.

  • Orosomucoid in urine predicts cardiovascular and over all mortality in patients with type ii diabetes
    Diabetologia, 2002
    Co-Authors: Merete Skovdal Christiansen, E Hommel, Erik Magid, Bo Feldtrasmussen
    Abstract:

    Aims/hypothesis: Urinary Orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary Orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes.

Jenny Sorensson - One of the best experts on this subject based on the ideXlab platform.

Erik Magid - One of the best experts on this subject based on the ideXlab platform.

  • increased urinary Orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes
    Journal of Diabetes and Its Complications, 2010
    Co-Authors: Merete Skovdal Christiansen, E Hommel, Erik Magid, Lars Friberg, Jens Molvig, Bo Feldtrasmussen
    Abstract:

    Abstract Objectives Increased urinary Orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients with type 2 diabetes and normal or increased UOER. Methods We performed a cross-sectional study of 40 patients with type 2 diabetes (normal UOER, n =16; increased UOER, n =24) who displayed no signs of cardiovascular disease and 21 healthy control persons. The renal clearance values of [ 51 Cr]ethylenediaminetetraacetic acid ([ 51 Cr]EDTA), lithium, Orosomucoid, albumin, and sodium were measured. Results Patients with type 2 diabetes had normal glomerular filtration rate (GFR) measured by [ 51 Cr]EDTA clearance. The clearance value of Orosomucoid was highly increased in patients with increased UOER. The clearance values of albumin were similar in patients with increased UOER and in healthy controls. Investigations of renal tubular function revealed normal and similar levels of lithium clearance and proximal and distal reabsorption of sodium and water. Serum values of Orosomucoid were higher in patients with increased UOER than in healthy controls ( P P Conclusions Patients with type 2 diabetes and increased UOER had normal GFR and showed no signs of renal glomerular or tubular dysfunction. We therefore hypothesize that increased levels of UOER may be caused by local renal production of Orosomucoid due to chronic low-grade inflammation.

  • increased urinary Orosomucoid excretion a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes
    Scandinavian Journal of Clinical & Laboratory Investigation, 2009
    Co-Authors: Michael Christiansen, E Hommel, Erik Magid, Jens Molvig, K Iversen, C T Larsen, Jens P Goetze, Bente Klarlund Pedersen, Bo Feldtrasmussen
    Abstract:

    Objective. In a previous study, urinary Orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. Material and methods. We performed a cross‐sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary Orosomucoid was measured using a particle‐enhanced immunoturbidimetric assay. Plasma interleukin‐6 (IL‐6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule‐1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants. Results. Patients with diabetes and increased U...

  • monitoring urinary Orosomucoid in acute inflammation observations on urinary excretion of Orosomucoid albumin α1 microglobulin and igg
    Clinical Chemistry, 2005
    Co-Authors: Erik Magid, Henrik Guldager, Dan Hesse, Merete Skovdal Christiansen
    Abstract:

    Background: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of Orosomucoid (α1-acid glycoprotein), albumin, α1-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. Methods: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. Results: During surgery-induced inflammation, the increase and decrease in Orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for Orosomucoid, 98-fold for α1-microglobulin, 33-fold for albumin, and 26-fold for IgG. Conclusions: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of Orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.

  • Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow up
    Diabetologia, 2005
    Co-Authors: Merete Skovdal Christiansen, E Hommel, Erik Magid, Bo Feldtrasmussen
    Abstract:

    Aims/hypothesis To study whether urinary Orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between Orosomucoid in serum and urine.

  • a particle enhanced turbidimetric immunoassay for quantitative determination of Orosomucoid in urine development validation and reference values
    Clinical Chemistry and Laboratory Medicine, 2004
    Co-Authors: Merete Skovdal Christiansen, Soren Blirupjensen, Lise Foged, Marianne Larsen, Erik Magid
    Abstract:

    Increased urinary Orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes, as demonstrated by a conventional, immunoturbidimetric method. We wanted to optimize the method by developing a fully automated, particle-enhanced turbidimetric (PET) immunoassay with a lower detection limit, to allow assessment of Orosomucoid in urine in healthy individuals and patients. A micro-particle-based immunoreagent was prepared for a PET immunoassay. The calibration was traceable to the certified reference material (CRM 470) for specific human serum proteins. We studied 69 healthy adults (28 men and 41 women) to establish reference values for the new assay. The detection limit of Orosomucoid in urine was found to be 0.05 mg/l, about 20 times lower than for the conventional assay. Within-run imprecision [CV%, (level)] was 6.7% (0.23 mg/l), 1.0% (1.08 mg/l) and 1.0% (4.69 mg/l). Total imprecision [CV%, (level)] was 10.4% (0.23 mg/l), 3.9% (1.08 mg/l) and 3.4% (4.69 mg/l). Reference values [median (2.5-97.5 percentiles)] for UOER were 0.36 (0.07-2.04) μg/min and for urinary Orosomucoid/creatinine ratio 0.04 (0.009-0.17) mg/mmol. We describe a fully automated, transferable, sufficiently precise, high-sensitivity assay for Orosomucoid in urine and present reference values traceable to CRM 470.