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Liss, Per
Publications (10 of 33) Show all publications
Liss, P., Hansell, P., Fasching, A. & Palm, F. (2016). Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide.. Upsala Journal of Medical Sciences, 121(1), 12-16
Open this publication in new window or tab >>Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide.
2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 12-16Article in journal (Refereed) Published
Abstract [en]

Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO2) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats. Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO2 was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase. Results Both CM reduced QO2 in human PTC (about -35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO2 (-34%). Both CM decreased QO2 in PTC from diabetic rats (-38% and -36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC. Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO2. Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-284721 (URN)10.3109/03009734.2016.1144664 (DOI)000372123700002 ()26933994 (PubMedID)
Funder
The Swedish Medical AssociationSwedish Diabetes AssociationSwedish Research Council
Available from: 2016-04-19 Created: 2016-04-19 Last updated: 2017-11-30Bibliographically approved
Nordquist, L., Friederich-Persson, M., Fasching, A., Liss, P., Shoji, K., Nangaku, M., . . . Palm, F. (2015). Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy. Journal of the American Society of Nephrology, 26(2), 328-338
Open this publication in new window or tab >>Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy
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2015 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 26, no 2, p. 328-338Article in journal (Refereed) Published
Abstract [en]

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glomerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharmacologic activation of the HIF system may prevent development of diabetic nephropathy.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-232171 (URN)10.1681/ASN.2013090990 (DOI)000348623700012 ()25183809 (PubMedID)
Available from: 2014-09-15 Created: 2014-09-15 Last updated: 2017-12-05Bibliographically approved
Gunnarsson, J., Dahlman, P., Helenius, M., Liss, P., Lönnemark, M., Magnusson, A. & Malmström, P.-U. (2015). Hematurispåret – en väg att snabbare diagnostisera blåscancer. Paper presented at Urologidagarna - 2015. Karlstad. Svensk Urologi (3), 38
Open this publication in new window or tab >>Hematurispåret – en väg att snabbare diagnostisera blåscancer
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2015 (Swedish)In: Svensk Urologi, no 3, p. 38-Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-264719 (URN)
Conference
Urologidagarna - 2015. Karlstad
Available from: 2015-10-15 Created: 2015-10-15 Last updated: 2015-10-15
Pihl, L., Nangaku, M., Inagi, R., Liss, P., Palm, F. & Nordquist, L. (2014). Pre-existing hypoxia sensitizes the kidney to an ischemia-reperfusion insult. Paper presented at EXPERIMENTAL BIOLOGY 2014 - Transforming the Future through Science, EB, April 26-30, 2014, Sand Diego, USA. The FASEB Journal, 28(1), Article ID 890.10.
Open this publication in new window or tab >>Pre-existing hypoxia sensitizes the kidney to an ischemia-reperfusion insult
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2014 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, no 1, article id 890.10Article in journal, Meeting abstract (Other academic) Published
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-246755 (URN)000346651003211 ()
Conference
EXPERIMENTAL BIOLOGY 2014 - Transforming the Future through Science, EB, April 26-30, 2014, Sand Diego, USA
Available from: 2015-03-10 Created: 2015-03-10 Last updated: 2017-12-04Bibliographically approved
Nordquist, L., Liss, P., Fasching, A., Hansell, P. & Palm, F. (2013). Hypoxia in the diabetic kidney is independent of advanced glycation end-products. Advances in Experimental Medicine and Biology, 765, 185-193
Open this publication in new window or tab >>Hypoxia in the diabetic kidney is independent of advanced glycation end-products
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2013 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 185-193Article in journal (Refereed) Published
Abstract [en]

Sustained hyperglycemia is closely associated with increased risk to develop nephropathy. We have previously reported alterations in the intrarenal oxygen metabolism already after the early onset of diabetes. Furthermore, formation of advanced glycation end-products (AGE) is postulated as a major contributor to diabetic nephropathy. We therefore investigated the possible relationship between altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and streptozotocin-diabetic rats with and without chronic treatment with aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N6-(1-Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was estimated by inulin clearance, oxygen tension (pO2) and interstitial pH by microelectrodes and regional renal blood flow (RBF) by laser-Doppler. Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration was unaffected by aminoguanidine, whereas L-NIL normalized GFR in diabetic rats. pO2 and interstitial pH, but not RBF, were lower in both kidney cortex and medulla compared to control rats, but was unaffected by both chronic treatments. Urinary protein excretion was higher in diabetic rats and unaffected by L-NIL, whereas aminoguanidine paradoxically increased this parameter. Damage scores were similar in all groups.In conclusion, diabetes-induced alterations in intrarenal oxygen metabolism are independent of the AGE pathway, and precede any morphological changes. These findings highlight the early stage of diabetes as being a metabolic disorder also in the kidney.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-182297 (URN)10.1007/978-1-4614-4989-8_26 (DOI)000339280100027 ()22879032 (PubMedID)
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2018-01-12Bibliographically approved
Liss, P., Cox, E. F., Eckerbom, P. & Francis, S. T. (2013). Imaging of intrarenal haemodynamics and oxygen metabolism. Clinical and experimental pharmacology & physiology, 40(2), 158-167
Open this publication in new window or tab >>Imaging of intrarenal haemodynamics and oxygen metabolism
2013 (English)In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 40, no 2, p. 158-167Article, review/survey (Refereed) Published
Abstract [en]

The interruption of blood flow results in impaired oxygenation and metabolism. This can lead to electrophysiological changes, functional impairment and symptoms in quick succession. Quantitative measures of organ perfusion, perfusion reserve and tissue oxygenation are crucial to assess normal tissue metabolism and function. Magnetic resonance imaging (MRI) provides a number of quantitative methods to assess physiology in the kidney. Blood oxygenation level-dependent (BOLD) MRI provides a method for the assessment of oxygenation. Blood flow to the kidney can be assessed using phase contrast MRI. Dynamic contrast-enhanced MRI and arterial spin labelling (ASL) provide methods to assess tissue perfusion, ASL using the magnetization of endogenous water protons and thus providing a non-invasive method to assess perfusion. The application of diffusion-weighted MRI allows molecular motion in the kidney to be measured. Novel techniques can also be used to assess oxygenation in the renal arteries and veins and, combined with flow measures, provide an estimation of oxygen metabolism. Magnetic resonance imaging provides a synergy of non-invasive techniques to study renal function and the demand for these techniques is likely to be driven by the incentive to avoid the use of contrast media, to avoid radiation and to avoid complications with intervention procedures.

Keywords
arterial spin labelling, blood oxygenation level dependent contrast, kidney, perfusion, renal blood flow, tissue oxygenation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-196139 (URN)10.1111/1440-1681.12042 (DOI)000314244300012 ()
Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2017-12-06Bibliographically approved
Eckerbom, P., Hansell, P., Bjerner, T., Palm, F., Weis, J. & Liss, P. (2013). Intravoxel Incoherent Motion MR Imaging of the Kidney: Pilot Study. Advances in Experimental Medicine and Biology, 765, 55-58
Open this publication in new window or tab >>Intravoxel Incoherent Motion MR Imaging of the Kidney: Pilot Study
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2013 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 55-58Article in journal (Refereed) Published
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.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-182298 (URN)10.1007/978-1-4614-4989-8_8 (DOI)000339280100009 ()22879014 (PubMedID)
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2017-12-07Bibliographically approved
Edlund, J., Fasching, A., Liss, P., Hansell, P. & Palm, F. (2010). The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney. Diabetes/Metabolism Research Reviews, 26(5), 349-356
Open this publication in new window or tab >>The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney
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2010 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 26, no 5, p. 349-356Article in journal (Refereed) Published
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.

Keywords
NADPH-oxidase, neuronal nitric oxide synthase, diabetes mellitus, oxygen consumption, oxidative stress
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135955 (URN)10.1002/dmrr.1099 (DOI)000280033900004 ()20583310 (PubMedID)
Available from: 2010-12-09 Created: 2010-12-09 Last updated: 2017-12-11Bibliographically approved
Liss, P., Hansell, P., Carlsson, P.-O., Fasching, A. & Palm, F. (2009). Iodinated contrast media decrease renomedullary blood flow. A possible cause of contrast media-induced nephropathy. Advances in Experimental Medicine and Biology, 645, 213-218
Open this publication in new window or tab >>Iodinated contrast media decrease renomedullary blood flow. A possible cause of contrast media-induced nephropathy
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2009 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 213-218Article in journal (Refereed) Published
Abstract [en]

The renal medulla has been implicated as a key target for contrast media-induced nephropathy (CIN). Although the effects of contrast media (CM) on whole kidney blood flow are well characterized, the effect of CM on renal medullary blood flow has been controversial. It has been reported that an extremely high dose of a high osmolar CM (iothalamate; 2900 mg I/kg bw) injected rapidly increased the renal outer medullary blood flow (OMBF). However, more clinical relevant doses consistently result in a sustained decrease in medullary blood flow. Furthermore, simultaneous measurements using both laser-Doppler flowmetry and hydrogen washout yield similar results of a decrease in OMBF after CM administration. CM induced a transient 28% decrease in the laser-Doppler signal from the outer medulla, while the hydrogen washout rate in the same region was reduced by approximately 50%. Furthermore, CM administration consistently results in decreased medullary oxygen tension (PO2). The renal medulla works already during normal physiological conditions at the verge of hypoxia, and the majority of the studies published so far are in agreement with the hypothesis that CIN may have its origin in a further reduction in blood flow and/or oxygen availability of this region of the kidney.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98480 (URN)10.1007/978-0-387-85998-9_33 (DOI)000262627100033 ()19227474 (PubMedID)
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2017-12-13Bibliographically approved
Edlund, J., Hansell, P., Fasching, A., Liss, P., Weis, J., Glickson, J. D. & Palm, F. (2009). Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging. Advances in Experimental Medicine and Biology, 645, 199-204
Open this publication in new window or tab >>Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging
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2009 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 199-204Article in journal (Refereed) Published
Abstract [en]

By applying invasive techniques for direct measurements of oxygen tension, we have reported decreased kidney oxygenation in experimental diabetes in rats. However, the non-invasive MRI technique utilizing the BOLD effect provides several advantages with the possibility to perform repetitive measurements in the same animals and in human subjects. In this study, we applied a modified single gradient echo micro-imaging sequence to detect the BOLD effect in kidneys of diabetic rats and compared the results to normoglycemic controls. All measurements were performed on inactin-anaesthetized adult male Wistar Furth rats. Diabetes was induced by streptozotocin (45 mg/kg) 14 days prior to MRI-analysis. Sixteen T2*-weighted image records (B0=1.5 T) were performed using radiofrequency spoiled gradient echo sequence with 2.6 ms step increments of TE (TE1=12 ms), while TR (75 ms) and bandwidth per pixel (71.4 Hz) were kept constant. T2* maps were computed by mono-exponential fitting of the pixel intensities. Relaxation rates R2* (1/T2*) in cortex and outer stripe of the outer medulla were similar in both groups (cortex for controls 22.3 +/- 0.4 vs. diabetics 23.1 +/- 1.8 Hz and outer stripe of outer medulla for controls 24.9 +/- 0.4 vs. diabetics 26.4 +/- 1.8 Hz; n=4 in both groups), whereas R2* was increased in the inner stripe of the outer medulla in diabetic rats (diabetics 26.1 +/- 2.4 vs. controls 18.8 +/- 1.4 Hz; n=4, P<0.05). This study demonstrates that experimental diabetes in rats induces decreased oxygenation of the renal outer medulla. Furthermore, the proposed T2*-weighted MR micro-imaging technique is suitable for detection of regional changes in kidney oxygenation in experimental animal models.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98482 (URN)10.1007/978-0-387-85998-9_31 (DOI)000262627100031 ()19227472 (PubMedID)
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2017-12-13
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