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  • 1.
    Eckerbom, Per
    et al.
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Bjerner, Tomas
    Uppsala universitet, Enheten för radiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Weis, Jan
    Uppsala universitet, Enheten för radiologi.
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Intravoxel Incoherent Motion MR Imaging of the Kidney: Pilot Study2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 55-58Article in journal (Refereed)
    Abstract [en]

    MR examinations (Achieva 3 T, Philips, Best, The Netherlands) were performed at five different occasions in a healthy volunteer (male 60 years) and in one renal cancer patient (male 78 years) with normal renal function (creatinine 88 μmol/L). Intravoxel incoherent motion (IVIM) coefficients D + D* were measured using respiratory-triggered diffusion-weighted spin-echo echo-planar imaging. Perfusion data of the patient were acquired using a saturation-recovery gradient-echo sequence and with the bolus of Gd-BOPTA (Multihance). D + D* were computed by monoexponential fitting of MR signal intensity attenuation versus b for b = 0, 50, 100, 150 s/mm2. Perfusion parameters were evaluated with “NordicICE” software. The map of D + D* was compared qualitatively with the perfusion map computed from the Gd scan. D + D* values of the cortex and medulla were in the range 2.3–2.7 and 1.1–1.6 × 10-3 mm2/s, respectively. In conclusion, in this pilot study a good qualitative relation between IVIM variables D + D* and renal perfusion has been found.

  • 2.
    Edlund, Jenny
    et al.
    Uppsala universitet, Integrativ Fysiologi.
    Fasching, Angelica
    Uppsala universitet, Integrativ Fysiologi.
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney2010In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 26, no 5, p. 349-356Article in journal (Refereed)
    Abstract [en]

    Background

    Sustained hyperglycaemia induces increased renal oxygen consumption resulting in reduced oxygen availability in the diabetic kidney. We investigated the roles of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the neuronal nitric oxide synthase (nNOS) for the increased oxygen consumption in streptozotocin-diabetic rats.

    Methods

    Oxygen consumption was measured in isolated proximal tubular cells (PTC) from streptozotocin-induced diabetic rats (n = 7-9 per group) with and without chronic treatment with apocynin, a NADPH-oxidase inhibitor, or S-methyl-L-thiocitrulline (SMTC), a selective nNOS inhibitor, or a combination of the two and the results were compared to normoglycaemic controls (n = 10). Oxidative stress was estimated from thiobarbituric acid reactive substances and protein expression measured by Western blot.

    Results

    Proximal tubular cells from untreated diabetic rats had increased oxygen consumption compared to controls (40.6 +/- 7.9 versus 10.9 +/- 2.0 nmol/mg protein/min). All treatments reduced the diabetes-induced increase in oxygen consumption (apocynin 10.5 +/- 1.7, SMTC 19.7 +/- 3.0 and apocynin +/- SMTC 21.6 +/- 3.6 nmol/mg protein/min). Neither apocynin nor SMTC had any effect on the oxygen consumption in cells pre-incubated with ouabain, an inhibitor of active electrolyte transport. Oxidative stress was elevated in the diabetic kidney and inhibited by all treatments. The increased oxygen consumption by diabetic proximal tubular cells correlated with increased protein expressions of p47phox and nNOS and the treatments prevented these increases.

    Conclusions

    Diabetes induces oxidative stress, which increases oxygen consumption in proximal tubular cells. Inhibition of either NADPH-oxidase or nNOS prevented the increased oxygen consumption. The effect of blocking both these enzymes was less than additive suggesting overlapping pathways which warrant further studies.

  • 3.
    Liss, Per
    et al.
    Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi.
    Aukland, Knut
    Carlsson, Per-Ola
    Institutionen för medicinsk cellbiologi.
    Palm, Fredrik
    Institutionen för medicinsk cellbiologi.
    Hansell, Peter
    Institutionen för medicinsk cellbiologi.
    Influence of iothalamate on renal medullary perfusion and oxygenation in the rat.2005In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 46, no 8, p. 823-9Article in journal (Other academic)
  • 4.
    Palm, Fredrik
    et al.
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Bergqvist, David
    Institutionen för kirurgiska vetenskaper.
    Carlsson, Per-Ola
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Hellberg, Olof
    Institutionen för medicinska vetenskaper.
    Nyman, Rickard
    Institutionen för onkologi, radiologi och klinisk immunologi.
    Hansell, Peter
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Liss, Per
    Institutionen för onkologi, radiologi och klinisk immunologi.
    The effects of carbon dioxide versus ioxaglate in the rat kidney.2005In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 16, no 2 Pt 1, p. 269-74Article in journal (Refereed)
  • 5.
    Palm, Fredrik
    et al.
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Buerk, Donald G.
    Carlsson, Per-Ola
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Hansell, Peter
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Liss, Per
    Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi.
    Reduced nitric oxide concentration in the renal cortex of streptozotocin-induced diabetic rats: effects on renal oxygenation and microcirculation2005In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, no 11, p. 3282-7Article in journal (Refereed)
    Abstract [en]

    Nitric oxide (NO) regulates vascular tone and mitochondrial respiration. We investigated the hypothesis that there is reduced NO concentration in the renal cortex of diabetic rats that mediates reduced renal cortical blood perfusion and oxygen tension (P O2). Streptozotocin-induced diabetic and control rats were injected with l-arginine followed by Nomega-nitro-L-arginine-metyl-ester (L-NAME). NO and P O2 were measured using microsensors, and local blood flow was recorded by laser-Doppler flowmetry. Plasma arginine and asymmetric dimethylarginine (ADMA) were analyzed by high-performance liquid chromatography. L-Arginine increased cortical NO concentrations more in diabetic animals, whereas changes in blood flow were similar. Cortical P O2 was unaffected by L-arginine in both groups. L-NAME decreased NO in control animals by 87 +/- 15 nmol/l compared with 45 +/- 7 nmol/l in diabetic animals. L-NAME decreased blood perfusion more in diabetic animals, but it only affected P O2 in control animals. Plasma arginine was significantly lower in diabetic animals (79.7 +/- 6.7 vs. 127.9 +/- 3.9 mmol/l), whereas ADMA was unchanged. A larger increase in renal cortical NO concentration after l-arginine injection, a smaller decrease in NO after L-NAME, and reduced plasma arginine suggest substrate limitation for NO formation in the renal cortex of diabetic animals. This demonstrates a new mechanism for diabetes-induced alteration in renal oxygen metabolism and local blood flow regulation.

  • 6.
    Palm, Fredrik
    et al.
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Fasching, Angelica
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Hansell, Peter
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Diabetes-induced decrease in renal oxygen tension: effects of an altered metabolism2006In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 578, p. 161-166Article in journal (Refereed)
    Abstract [en]

    During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

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