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Gustafsson, Håkan
Publications (10 of 45) Show all publications
Schiffer, T., Gustafsson, H. & Palm, F. (2018). Kidney outer medulla mitochondria are more efficient compared with cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment. American Journal of Physiology - Renal Physiology, 315(3), F677-F681
Open this publication in new window or tab >>Kidney outer medulla mitochondria are more efficient compared with cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment
2018 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 315, no 3, p. F677-F681Article in journal (Refereed) Published
Abstract [en]

The kidneys receive similar to 25% of cardiac output, which is a prerequisite to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences, in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney, may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is related to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla function at the verge of hypoxia, and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats by using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient, and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC, 2018
Keywords
cortex; kidney; medulla; mitochondria; oxygen affinity; P/O ratio
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-151482 (URN)10.1152/ajprenal.00207.2018 (DOI)000444017300015 ()29846107 (PubMedID)
Note

Funding Agencies|Swedish Medical Research Council; Swedish Diabetes Foundation; Swedish Research Council; Family Ernfors Foundation

Available from: 2018-09-24 Created: 2018-09-24 Last updated: 2018-12-10
Franzén, S., Pihl, L., Khan, N., Gustafsson, H. & Palm, F. (2016). Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice. American Journal of Physiology - Renal Physiology, 310(9), F807-F809
Open this publication in new window or tab >>Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice
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2016 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 310, no 9, p. F807-F809Article in journal (Refereed) Published
Abstract [en]

Intrarenal tissue hypoxia has been proposed as a unifying mechanism for the development of chronic kidney disease, including diabetic nephropathy. However, hypoxia has to be present before the onset of kidney disease in order to be the causal mechanism. In order to establish if hypoxia precedes the onset of diabetic nephropathy, we implemented a minimally invasive electron paramagnetic resonance oximetry technique using implanted oxygen sensing probes for repetitive measurements of in vivo kidney tissue oxygen tensions in mice. Kidney cortex oxygen tensions were measured before and up to 15 days after the induction of insulinopenic diabetes in male mice and compared to normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined in order to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia three days after the induction of diabetes, which persisted throughout the study period. On day 16, diabetic mice had glomerular hyperfiltration, but normal urinary albumin excretion. In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy.

Place, publisher, year, edition, pages
American Physiological Society Journals, 2016
Keywords
nephropathy, diabetes, hypoxia, EPR
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-125526 (URN)10.1152/ajprenal.00049.2016 (DOI)000375115700001 ()
Note

The status of this article was previous Manuscript.

Funding agencies: Swedish Research Council; Swedish Heart Lung Foundation; Swedish Diabetes Foundation

Available from: 2016-02-26 Created: 2016-02-25 Last updated: 2018-10-01Bibliographically approved
Ivarsson, M., Broman, C., Gustafsson, H. & Holm, N. G. (2015). Biogenic Mn-Oxides in Subseafloor Basalts. PLoS ONE, 10(6), e0128863
Open this publication in new window or tab >>Biogenic Mn-Oxides in Subseafloor Basalts
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, p. e0128863-Article in journal (Refereed) Published
Abstract [en]

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120354 (URN)10.1371/journal.pone.0128863 (DOI)000356932500031 ()26107948 (PubMedID)
Note

Funding Agencies|Swedish Research Council [2012-4364]; Danish National Research Foundation [DNRF53]

Available from: 2015-07-31 Created: 2015-07-31 Last updated: 2017-12-04
Lilledahl, M. B., Gustafsson, H., Gunnar Ellingsen, P., Zachrisson, H., Hallbeck, M., Stenhjem Hagen, V., . . . Lindgren, M. (2015). Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques. Journal of Biomedical Optics, 20(2), 020503
Open this publication in new window or tab >>Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques
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2015 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 2, p. 020503-Article in journal (Refereed) Published
Abstract [en]

Human atherosclerotic samples collected by carotid endarterectomy were investigated using electronic paramagnetic resonance imaging (EPRI) for visualization of reactive oxygen species, and nonlinear optical microscopy (NLOM) to study structural features. Regions of strong EPRI signal, indicating a higher concentration of reactive oxygen species and increased inflammation, were found to colocalize with regions dense in cholesterol crystals as revealed by NLOM.

Place, publisher, year, edition, pages
Society of Photo-optical Instrumentation Engineers (SPIE), 2015
Keywords
atherosclerosis; electronic paramagnetic resonance imaging; polarimetry; nonlinear optical microscopy
National Category
Clinical Medicine Chemical Sciences Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-116839 (URN)10.1117/1.JBO.20.2.020503 (DOI)000350462900003 ()25714991 (PubMedID)
Note

Funding Agencies|Swedish Research Council [diarienr 2009-5430]

Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2018-01-11
Adolfsson, E., White, S., Landry, G., Lund, E., Gustafsson, H., Verhaegen, F., . . . Alm Carlsson, G. (2015). Measurement of absorbed dose to water around an electronic brachytherapy source: Comparison of two dosimetry systems: lithium formate EPR dosimeters and radiochromic EBT2 film. Physics in Medicine and Biology, 60(9), 3869-3882
Open this publication in new window or tab >>Measurement of absorbed dose to water around an electronic brachytherapy source: Comparison of two dosimetry systems: lithium formate EPR dosimeters and radiochromic EBT2 film
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2015 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 9, p. 3869-3882Article in journal (Refereed) Published
Abstract [en]

Interest in high dose rate (HDR) electronic brachytherapy operating at 50 kV is increasing. For quality assurance it is important to identify dosimetry systems that can measure the absorbed doses in absolute terms which is difficult in this energy region. In this work a comparison is made between two dosimetry systems, EPR lithium formate dosimeters and radiochromic EBT2 film.

Both types of dosimeters were irradiated simultaneously in a PMMA phantom using the Axxent EBS. Absorbed dose to water was determined at distances of 10 mm, 30 mm and 50 mm from the EBS. Results were traceable to different primary standards as regards to absorbed dose to water (EPR) and air kerma (EBT2). Monte Carlo simulations were used in absolute terms as a third estimate of absorbed dose to water.

Agreement within the estimated expanded (k = 2) uncertainties (5% (EPR), 7% (EBT2)) was found between the results at 30 mm and 50 mm from the x-ray source. The same result was obtained in 4 repetitions of irradiation, indicating high precision in the measurements with both systems. At all distances, agreement between EPR and Monte Carlo simulations was shown as was also the case for the film measurements at 30mm and 50mm. At 10mm the geometry for the film measurements caused too large uncertainty in measured values depending on the exact position (within sub-mm distances) of the EBS and the 10 mm film results were exculded from comparison.

This work has demonstrated good performance of the lithium formate EPR dosimetry system in accordance with earlier experiments at higher photon energies (192Ir HDR brachytherapy). It was also highlighted that there might be issues regarding the energy dependence and intrinsic efficiency of the EBT2 film that need to be considered for measurements using low energy sources.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2015
Keywords
Electronic brachytherapy, EPR, lithium formate, radiochromic film, intrinsic efficiency
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-111090 (URN)10.1088/0031-9155/60/9/3869 (DOI)000354104700030 ()
Available from: 2014-10-07 Created: 2014-10-07 Last updated: 2017-12-05Bibliographically approved
Gustafsson, H., Hallbeck, M., Lindgren, M., Kolbun, N., Jonson, M., Engström, M., . . . Zachrisson, H. (2015). Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging. Magnetic Resonance in Medicine, 73(4), 1682-1691
Open this publication in new window or tab >>Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
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2015 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, no 4, p. 1682-1691Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113407 (URN)10.1002/mrm.25267 (DOI)000351685900035 ()24753234 (PubMedID)
Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2017-12-05
Berg, K., Ericsson, M., Lindgren, M. & Gustafsson, H. (2014). A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies. PLoS ONE, 9(3)
Open this publication in new window or tab >>A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3Article in journal (Refereed) Published
Abstract [en]

Objective

An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetr​amethylpyrrolidine(CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies.

Materials and Methods

Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP•) with known spin concentration.

Results

The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k = 1). The spin concentration of samples stored at −80°C could be reproduced after 6 months of storage well within the same error estimate.

Conclusion

The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105262 (URN)10.1371/journal.pone.0090964 (DOI)000332483600116 ()24603936 (PubMedID)
Available from: 2014-03-14 Created: 2014-03-14 Last updated: 2017-12-05Bibliographically approved
Adolfsson, E., Gustafsson, H., Lund, E., Alm Carlsson, G., Olsson, S. & Carlsson Tedgren, Å. (2014). A system for remote dosimetry audit of 3D-CRT, IMRT and VMAT based on lithium formate dosimetry. Radiotherapy and Oncology, 113(2), 279-282
Open this publication in new window or tab >>A system for remote dosimetry audit of 3D-CRT, IMRT and VMAT based on lithium formate dosimetry
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2014 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 113, no 2, p. 279-282Article in journal (Refereed) Published
Abstract [en]

The aim of this work was to develop and test a remote end-to-end audit system using lithium formate EPR dosimeters. Four clinics were included in a pilot study, absorbed doses determined in the PTV agreed with TPS calculated doses within ±5% for 3D-CRT and ±7% (k=1) for IMRT/VMAT dose plans.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Dosimetry audit; remote audit; end-to-end; EPR; ESR; lithium formate
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-111089 (URN)10.1016/j.radonc.2014.11.027 (DOI)000347657200021 ()
Available from: 2014-10-07 Created: 2014-10-07 Last updated: 2017-12-05Bibliographically approved
Fattibene, P., Trompier, F., Wieser, A., Brai, M., Ciesielski, B., De Angelis, C., . . . Tuner, H. (2014). EPR dosimetry intercomparison using smart phone touch screen glass. Radiation and Environmental Biophysics, 53(2), 311-320
Open this publication in new window or tab >>EPR dosimetry intercomparison using smart phone touch screen glass
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2014 (English)In: Radiation and Environmental Biophysics, ISSN 0301-634X, E-ISSN 1432-2099, Vol. 53, no 2, p. 311-320Article in journal (Refereed) Published
Abstract [en]

This paper presents the results of an interlaboratory comparison of retrospective dosimetry using the electron paramagnetic resonance method. The test material used in this exercise was glass coming from the touch screens of smart phones that might be used as fortuitous dosimeters in a large-scale radiological incident. There were 13 participants to whom samples were dispatched, and 11 laboratories reported results. The participants received five calibration samples (0, 0.8, 2, 4, and 10 Gy) and four blindly irradiated samples (0, 0.9, 1.3, and 3.3 Gy). Participants were divided into two groups: for group A (formed by three participants), samples came from a homogeneous batch of glass and were stored in similar setting; for group B (formed by eight participants), samples came from different smart phones and stored in different settings of light and temperature. The calibration curves determined by the participants of group A had a small error and a critical level in the 0.37-0.40-Gy dose range, whereas the curves determined by the participants of group B were more scattered and led to a critical level in the 1.3-3.2-Gy dose range for six participants out of eight. Group A were able to assess the dose within 20 % for the lowest doses (< 1.5 Gy) and within 5 % for the highest doses. For group B, only the highest blind dose could be evaluated in a reliable way because of the high critical values involved. The results from group A are encouraging, whereas the results from group B suggest that the influence of environmental conditions and the intervariability of samples coming from different smart phones need to be further investigated. An alongside conclusion is that the protocol was easily transferred to participants making a network of laboratories in case of a mass casualty event potentially feasible.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2014
Keywords
EPR dosimetry, Radiological emergency, Retrospective dosimetry, Glass
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-111969 (URN)10.1007/s00411-014-0533-x (DOI)000334998200011 ()24671362 (PubMedID)
Available from: 2014-11-12 Created: 2014-11-12 Last updated: 2017-12-05Bibliographically approved
Lund, E., Adolfsson, E., Kolbun, N. & Gustafsson, H. (2014). EPR imaging of dose distributions aiming at applications in radiation therapy. Radiation Protection Dosimetry, 159(1-4), 130-136
Open this publication in new window or tab >>EPR imaging of dose distributions aiming at applications in radiation therapy
2014 (English)In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 159, no 1-4, p. 130-136Article in journal (Refereed) Published
Abstract [en]

A one-dimensional electron paramagnetic resonance (EPR) imaging method for visualisation of dose distributions in photon fields has been developed. Pressed pellets of potassium dithionate were homogeneously irradiated in a Co-60 radiation field to 600 Gy. The EPR analysis was performed with an X-Band (9.6 GHz) Bruker E540 EPR and EPR imaging spectrometer equipped with an E540 GC2X two-axis X-band gradient coil set with gradients along the y axis (along the sample tube) and z axis (along B-0) and an ER 4108TMHS resonator. Image reconstruction, including deconvolution, baseline corrections and corrections for the resonator sensitivity, was performed using an in-house-developed Matlab code for the purpose to have a transparent and complete algorithm for image reconstruction. With this method, it is possible to visualise a dose distribution with an accuracy of similar to 5 % within +/- 5 mm from the centre of the resonator.

Place, publisher, year, edition, pages
Oxford University Press, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109275 (URN)10.1093/rpd/ncu142 (DOI)000338829100018 ()24757173 (PubMedID)
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
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