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| 2. |
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| 3. |
- Palm, Fredrik, 1973-, et al.
(författare)
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Sociologik : Tio essäer om socialitet och tänkande
- 2011. - 1
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- "Det sociala" tillhör de begrepp som samhällsvetenskapen utgår från men sällan känner något behov av att förklara. Ofta är socialiteten den samhällsvetenskapliga praktikens utgångspunkt och mål, men dess innebörd kan inte fastställas utan att överskrida gränserna till t.ex. filosofi, historia och religion. Kanske är avsaknaden av en kontinuerlig reflektion över det socialas innebörd rent av ett försvar av det samhällsvetenskapliga fältet. I denna bok diskuterar tio samhällsvetare och humanister det socialas betydelse från Immanuel Kant till Slavoj Zizek. Det handlar om tio sätt att tänka kring det sociala, om tio sociologiker. Detta skulle kunna tolkas som att det sociala är det objekt bokens olika bidrag behandlar ur respektive perspektiv. Men det kan också ges en snävare tolkning. Det verkliga objektet för undersökningarna blir då själva relationen mellan det sociala och vetandet. Med detta synsätt kan det sociala inte uppfattas som ett neutralt eller autonomt faktum utanför tänkandet. Snarare blir socialiteten något som framträder först i vetandets konkreta gränsdragningar och skillnadsskapanden. Denna bok är ett mångbottnat bidrag till diskussionen om vad samhället är och om möjligheterna att förändra det. Medverkande författare: Christian Abrahamsson, Magnus Fiskesjö, Maria Johansen, Per Magnus Johansson, Vessela Misheva, Gunnar Olsson, Fredrik Palm, Olli Pyyhtinen, Anders Ramsay och Sverre Wide
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| 4. |
- Palm, Fredrik, 1973-, et al.
(författare)
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Transparency and visualization in Text mining : A case study of Connected Concept analysis with Textometrica
- 2013
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Konferensbidrag (refereegranskat)abstract
- In the digital age, large amounts of text date are increasingly available. Information visualization has become an important approach for handling these large datasets. But a critical perspective is still required in the process of analyzing data, as well as in the communication of methods and results.The researcher must ensure that the approaches provide the quality, transparency and precision needed for the research questions to be answered. In this paper we will report about a case study of the research method Connected Concept Analysis (Lindgren 2011) and the design of the tool Textometrica (Lindgren & Palm 2012).
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| 5. |
- Schnermann, Jurgen, et al.
(författare)
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Erik Persson (1941-2020) : a Remembrance
- 2020
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 230:4
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 6. |
- Wide, Sverre, 1973-, et al.
(författare)
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Inledning
- 2011
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Ingår i: Sociologik. - Stockholm : Santérus Academic Press. - 9789173590266 ; , s. 9-35
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Bokkapitel (refereegranskat)
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| 7. |
- Backman, Fredrik
(författare)
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Energy efficiency in Swedish SMEs : Exploring barriers, knowledge creation and the role of municipal energy efficiency programs
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis is to analyze how municipalities support small and medium-sized enterprises (SMEs) in their work to improve their energy efficiency. The purpose of this study is to increase the current understanding of how the methods and tools used by municipalities to assist SMEs in improving their energy efficiency influence the end results in terms of achieved energy efficiency, and how knowledge related to energy efficiency is created within SMEs. This thesis consists of two separate case studies that examine how two municipalities used a network approach to support SMEs in implementing energy efficient measures. The theoretical frameworks of policy networks, barriers, communities of practice (COPs), and energy efficiency networks were used in this thesis. The findings are presented in the appended four articles. An overall conclusion is that networks that provide information in the form of a report with technological solutions as the only output are less likely to reach the agreed-upon goals. To achieve a more successful result, SMEs must be active in the process; they must be allowed to create knowledge and understanding that they perceive as valuable and relevant for themselves. Another important result is that information is not automatically transformed by SMEs into knowledge. In fact, SMEs need a platform from which they can negotiate the received information and use it to create knowledge through practice and social interaction. Finally, it was found that the type of technological solution is not insignificant; the type of energy efficient measure to be implemented and its level of complexity affect how a municipality should support energy efficiency work among SMEs.
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| 8. |
- Berg, Christoffer, 1986-
(författare)
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Public Planning, Neoliberal Hybridity and Local Activism in Sundbyberg : Epochal Reconfiguration of Urban Development in Greater Stockholm
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Which urban policy responses are deployed when a small social democratic municipality in a greater city region aims to be competitive for private investments in housing and the built environment? Which new institutional development arrangements are implemented for this purpose, in the wake of a decades-long hegemonic position of the municipal public housing company? This thesis draws on a qualitative case study design to approach such questions, and investigates recent urban development in Sundbybergs stad in Greater Stockholm to answer them. Theoretically, the thesis draws on a theory of neoliberal localization in combination with Henri Lefebvre’s theory of the social production of space. The thesis is thereby able to explain how the municipality consolidated political power, institutional infrastructures, and administrative capacities with a view to introducing a market-based paradigm of urban development. It argues that this paradigm became characterized by a neoliberal hybridity. It supports this argument by analyzing three major development projects targeting three areas with very different sociospatial characteristics. The thesis thereby demonstrates how market-based developments integrated a number of regulatory features and public planning interventions in accordance with certain objectives, concerns, and conditions. E.g., it reveals how the development of a 1970s Million Homes Programme area, Hallonbergen, relied both on an extended sale of public assets to support private developers’ investments with the objective of comprehensively transforming the area, and on extraordinary measures for ‘social sustainability’. It also reveals how the development of the original municipal town, Central Sundbyberg, was arranged in a municipal development company. This established a business-like format for political control and external expertise, while undermining public planning and clouding democratic accountability. This point is further emphasized by analyzing local inhabitants’ methods for contesting certain development features and land use proposals in this project, enforcing a re-politicization of a largely depoliticized development project. Ultimately, the thesis contributes new knowledge on the variegating forms of neoliberal urbanism through an atypical case of a subordinate city region municipality that historically has been characterized by social democracy, a large public rental housing structure, a public housing company with control of spatial planning, and working-class populations and industries.
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| 9. |
- Bergman, Hilde-Marlene, et al.
(författare)
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Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
- 2019
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 411:13, s. 2809-2816
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.
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| 10. |
- Buckland, Philip I., 1973-, et al.
(författare)
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The Strategic Environmental Archaeology Database : a resource for international, multiproxy and transdisciplinary studies of environmental and climatic change
- 2015
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Konferensbidrag (refereegranskat)abstract
- Climate and environmental change are global challenges which require global data and infrastructure to investigate. These challenges also require a multi-proxy approach, integrating evidence from Quaternary science and archaeology with information from studies on modern ecology and physical processes among other disciplines. The Strategic Environmental Archaeology Database (SEAD http://www.sead.se) is a Swedish based international research e-infrastructure for storing, managing, analysing and disseminating palaeoenvironmental data from an almost unlimited number of analysis methods. The system currently makes available raw data from over 1500 sites (>5300 datasets) and the analysis of Quaternary fossil insects, plant macrofossils, pollen, geochemistry and sediment physical properties, dendrochronology and wood anatomy, ceramic geochemistry and bones, along with numerous dating methods. This capacity will be expanded in the near future to include isotopes, multi-spectral and archaeo-metalurgical data. SEAD also includes expandable climate and environment calibration datasets, a complete bibliography and extensive metadata and services for linking these data to other resources. All data is available as Open Access through http://qsead.sead.se and downloadable software. SEAD is maintained and managed at the Environmental Archaeology Lab and HUMlab at Umea University, Sweden. Development and data ingestion is progressing in cooperation with The Laboratory for Ceramic Research and the National Laboratory for Wood Anatomy and Dendrochronology at Lund University, Sweden, the Archaeological Research Laboratory, Stockholm University, the Geoarchaeological Laboratory, Swedish National Historical Museums Agency and several international partners and research projects. Current plans include expanding its capacity to serve as a data source for any system and integration with the Swedish National Heritage Board's information systems. SEAD is partnered with the Neotoma palaeoecology database (http://www.neotomadb.org) and a new initiative for building cyberinfrastructure for transdisciplinary research and visualization of the long-term human ecodynamics of the North Atlantic funded by the National Science Foundation (NSF).
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| 11. |
- Burmakin, Mikhail, et al.
(författare)
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Pharmacological HIF-PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
- 2021
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 233:1
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Hypoxia-inducible factors (HIFs) are O2 -sensitive transcription factors that regulate multiple biological processes which are essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF-prolyl hydroxylase domain (PHD) dioxygenases (HIF-PHIs) activate HIF-dependent transcriptional programs and have broad clinical potential. HIF-PHIs are currently in global late-stage clinical development for the treatment of anaemia associated with chronic kidney disease. Although the effects of hypoxia on renal haemodynamics and function have been studied in animal models and in humans living at high altitude, the effects of pharmacological HIF activation on renal haemodynamics, O2 metabolism and metabolic efficiency are not well understood.METHODS: Using a cross-sectional study design, we investigated renal haemodynamics, O2 metabolism, gene expression and NO production in healthy rats treated with different doses of HIF-PHIs roxadustat or molidustat compared to vehicle control.RESULTS: Systemic administration of roxadustat or molidustat resulted in a dose-dependent reduction in renovascular resistance (RVR). This was associated with increased glomerular filtration rate (GFR), urine flow and tubular sodium transport rate (TNa ). Although both total O2 delivery and TNa were increased, more O2 was extracted per transported sodium in rats treated with high-doses of HIF-PHIs, suggesting a reduction in metabolic efficiency. Changes in RVR and GFR were associated with increased nitric oxide (NO) generation and substantially suppressed by pharmacological inhibition of NO synthesis.CONCLUSIONS: Our data provide mechanistic insights into dose-dependent effects of short-term pharmacological HIF activation on renal haemodynamics, glomerular filtration and O2 metabolism and identify NO as a major mediator of these effects.
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| 12. |
- Carlsson, Per-Ola, et al.
(författare)
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Chronically decreased oxygen tension in rat pancreatic islets transplantedunder the kidney capsule
- 2000
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 69:5, s. 761-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. This study measured the oxygen tension and blood perfusion in 1-, 2-, and 9-month-old islet grafts. METHODS: The partial pressure of oxygen was measured in pancreatic islets transplanted beneath the renal capsule of diabetic and nondiabetic recipient rats with a modified Clark electrode (outer tip diameter 2-6 microm). The size of the graft (250 islets) was by purpose not large enough to cure the diabetic recipients. The oxygen tension in islets within the pancreas was also recorded. Blood perfusion was measured with the laser-Doppler technique. RESULTS: Within native pancreatic islets, the partial pressure of oxygen was approximately 40 mm Hg (n=8). In islets transplanted to nondiabetic animals, the oxygen tension was approximately 6-7 mm Hg 1, 2, and 9 months posttransplantation. No differences could be seen between the different time points after transplantation. In the diabetic recipients, an even more pronounced decrease in graft tissue oxygen tension was recorded. The mean oxygen tension in the superficial renal cortex surrounding the implanted islets was similar in all groups (approximately 15 mm Hg). Intravenous administration of glucose (0.1 gxkg(-1)x min(-1)) did not affect the oxygen tension in any of the investigated tissues. The islet graft blood flow was similar in all groups, measuring approximately 50% of the blood flow in the kidney cortex. CONCLUSION: The oxygen tension in islets implanted beneath the kidney capsule is markedly lower than in native islets up to 9 months after transplantation. Moreover, persistent hyperglycemia in the recipient causes an even further decrease in graft oxygen tension, despite similar blood perfusion. To what extent this may contribute to islet graft failure remains to be determined.
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| 13. |
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| 14. |
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| 15. |
- Carvalho, Carla, 1988-
(författare)
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The Role of Kidney Oxygen Homeostasis for the Development of Kidney Disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The relation between oxygen supply and demand determines tissue oxygen tension (PO2). When intrarenal tissue PO2 decreases, any compensatory increase in oxygen supply via increased renal blood flow is likely to increase glomerular filtration rate. The resulting increased tubular load of electrolytes destined for active transport increases oxygen consumption, thus affecting intrarenal tissue PO2. Consequently, the kidney is particularly sensitive to alterations in oxygen homeostasis and kidney hypoxia is acknowledged as a common pathway to end stage renal disease. Different factors that can affect intrarenal oxygen homeostasis, including alterations in blood pressure and sodium intake dietary or pathologies such as diabetes mellitus, anemia or atherosclerosis. This thesis focuses on understanding how these factors influence kidney oxygen homeostasis.Pronounced reduction in sodium intake caused tissue hypoxia in kidney cortex via activation of the renin-angiotensin-aldosterone leading to increased tubular sodium reabsorption. Angiotensin II and aldosterone affect kidney oxygen handling differently. Whereas angiotensin II mainly affects kidney oxygen delivery, aldosterone mainly affects oxygen consumption.The hypoxia-inducible factor (HIF) system is a cellular defense mechanism against prolonged hypoxia. Although diabetes causes intrarenal hypoxia, hyperglycemia per se also prevents HIF-activation. Therefore, the effects of type 1 diabetes were evaluated in genetically modified mice with chronic HIF-activation. Diabetic mice with globally increased HIF activity, due to heterozygote prolyl hydroxylase-2 deficiency, displayed reduced mitochondria leak respiration and preserved cortical PO2. Diabetic mice with kidney-specific HIF activation, due to homozygous deficiency of von Hippel-Lindau, developed reduced mitochondria leak respiration and reduced urinary albumin excretion.The normal age-related decline in kidney function has been proposed to be due to, at least in part, increased oxidative stress, which can induce mitochondrial leak respiration via activation of uncoupling proteins. Indeed, two-year old mice deficient of uncoupling protein-2 presented with improved mitochondria efficiency and reduced urinary protein excretion.Summarizing, the data presented in this thesis provide clear support for potent influence of the renin-angiotensin-aldosterone system, HIF activation and mitochondria function on intrarenal oxygen availability. Maintaining kidney oxygen homeostasis may be a unifying strategy to protect kidney function.
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| 16. |
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| 17. |
- Christensen, Michael, et al.
(författare)
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Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein-2
- 2019
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Ingår i: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 35:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of the study is to examine the effect of metformin on oxygen metabolism and mitochondrial function in the kidney of an animal model of insulinopenic diabetes in order to isolate any renoprotective effect from any concomitant effect on blood glucose homeostasis.Methods: Sprague-Dawley rats were injected with streptozotocin (STZ) (50 mg kg(-1)) and when stable started on metformin treatment (250 mg kg(-1)) in the drinking water. Rats were prepared for in vivo measurements 25 to 30 days after STZ injection, where renal function, including glomerular filtration rate and sodium transport, was estimated in anesthetized rats. Intrarenal oxygen tension was measured using oxygen sensors. Furthermore, mitochondrial function was assessed in mitochondria isolated from kidney cortex and medulla analysed by high-resolution respirometry, and superoxide production was evaluated using electron paramagnetic resonance.Results: Insulinopenic rats chronically treated with metformin for 4 weeks displayed improved medullary tissue oxygen tension despite of no effect of metformin on blood glucose homeostasis. Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats.Conclusions: Metformin attenuates diabetes-induced renal medullary tissue hypoxia in an animal model of insulinopenic type 1 diabetes. The results suggest that the mechanistic pathway to attenuate the diabetes-induced medullary hypoxia is independent of blood glucose homeostasis and includes reduced UCP2-mediated mitochondrial proton LEAK.
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| 18. |
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| 19. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging
- 2020
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 319:6, s. F966-F978
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Tidskriftsartikel (refereegranskat)abstract
- Circadian regulation of kidney function is involved in maintaining whole body homeostasis, and dysfunctional circadian rhythm can potentially be involved in disease development. Magnetic resonance imaging (MRI) provides reliable and reproducible repetitive estimates of kidney function noninvasively without the risk of adverse events associated with contrast agents and ionizing radiation. The purpose of this study was to estimate circadian variations in kidney function in healthy human subjects with MRI and to relate the findings to urinary excretions of electrolytes and markers of kidney function. Phase-contrast imaging, arterial spin labeling, and blood oxygen level-dependent transverse relaxation rate (R2*) mapping were used to assess total renal blood flow and regional perfusion as well as intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24-h period. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24 h, with increasing flow from noon to midnight and decreasing flow during the night. In contrast, no circadian variation in intrarenal oxygenation was detected. Urinary excretions of electrolytes, osmotically active particles, creatinine, and urea all displayed circadian variations, peaking during the afternoon and evening hours. In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation.
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| 20. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
- 2019
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:4, s. F693-F702
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 females, 13 males), Arterial Spin Labeling (ASL) to estimate regional renal perfusion, Blood Oxygen Level Dependent (BOLD) transverse relaxation rate (R2*) to estimate oxygenation, and Apparent Diffusion Coefficient (ADC), true diffusion (D) and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex, outer and inner medulla. Additionally, phase contrast (PC) MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index and renal volume. Similar patterns in all investigated parameters were observed in females and males. In conclusion, non-invasive MRI provides useful tools to evaluate intra renal differences in blood flow, perfusion, diffusion, oxygenation and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.
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| 21. |
- Edlund, Lars-Erik, 1953-, et al.
(författare)
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Diabas – nordisk ordgeografisk databas
- 2012
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Annan publikation (populärvet., debatt m.m.)abstract
- Diabas – North Germanic geolexical database Online database to explore, visualize words in North Germanic dialects with dynamic maps, tables etc. Login required, contact Authors for permission
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| 22. |
- Edwards, Aurelie, et al.
(författare)
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A model of mitochondrial O-2 consumption and ATP generation in rat proximal tubule cells
- 2020
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Ingår i: American Journal of Physiology - Renal Physiology. - : AMER PHYSIOLOGICAL SOC. - 1931-857X .- 1522-1466. ; 318:1, s. F248-F259
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen tension in the kidney is mostly determined by O-2 consumption (Qo(2)), which is, in turn, closely linked to tubular Na+ reabsorption. The objective of the present study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between Qo(2), ATP formation (G(ATP)), ATP hydrolysis (QATP), and Na+ transport in the PH. The present model correctly predicts in vitro and in vivo measurements of Qo(2), Owns, and ATP and P-i concentrations in PT cells. Our simulations suggest that O-2 levels are not rate limiting in the proximal convoluted tubule, absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the G AT p-to-Qo(2) ratio, a key determinant of the number of Na+ moles actively reabsorbed per mole of O-2 consumed. An isolated increase in QATP or in cytoplasmic pH raises the GAS-to-Qo(2) ratio. Thus. variations in Na+ reabsorption and pH along the PT may, per se, generate axial heterogeneities in the efficiency of mitochondria' metabolism and Na+ transport. Our results also indicate that the G(AT)(P)-to-Qo(2) ratio is strongly impacted not only by H+ leak permeability. which reflects mitochondrial uncoupling, but also by K+ leak pathways. Simulations suggest that the negative impact of increased uncoupling in the diabetic kidney on mitochondrial metabolic efficiency is partly counterbalanced by increased rates of Na+ transport and ATP consumption. This model provides a framework to investigate the role of mitochondrial dysfunction in acute and chronic renal diseases.
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| 23. |
- Ek, Sverker R, 1930-, et al.
(författare)
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Hjalmar Bergman : korrespondenser 1900-1930
- 2012
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Annan publikation (populärvet., debatt m.m.)abstract
- Hjalmar Bergman (19/9 1883-1/1 1931) är en framträdande och särpräglad författarprofil i svensk litteratur under förra hälften av 1900-talet. Hans rika produktion omfattar inte bara romaner, noveller och dramer utan även sagor, filmmanuskript, radiopjäser och översättningar. Bergman var också en tämligen flitig brevskrivare. Hans korrespondens finns till stora delar bevarad på olika arkiv och bibliotek i in- och utlandet. Här har publicerats enbart breven till vänner och samtida kulturpersonligheter (se nedan). De presenteras digitalt som en samlad textcorpus. Samtliga brevformer som vykort, telegram, visitkort har medtagits. I de fall där originalbreven saknar angivelser av avsändningsort och/eller datum har dessa uppgifter tentativt kompletterats inom klammer.Publiceringen syftar till att vara en digital forskningsresurs där breven kan lokaliseras på flertal olika sätt. Dessutom sätts brev i kontext då man enkelt kan se vilka verk, personer m.m. som förekommer i varje brev.För att orientera sig i materialet finns ett antal ingångar:Utforska breven utifrån adressaterUtforska breven utifrån vilka personer som förekommer i brevenUtforska utifrån vilkav erk som är omnämnda i brevenUtforska utifrån breven utifrån verkens genrer
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| 24. |
- Elksnis, Andris, et al.
(författare)
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Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK
- 2021
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Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 135:19, s. 2243-2263
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Tidskriftsartikel (refereegranskat)abstract
- The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of non-obese diabetic (NOD) mice with imatinib resulted in increased beta-cell AMP-activated kinase (AMPK) phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against islet amyloid polypeptide (IAPP)-aggregation, thioredoxin interacting protein (TXNIP) up-regulation and beta-cell death. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme enoyl coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1). In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and acyl-CoA carboxylase (ACC) phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP down-regulation, which in turn protects against beta-cell death.
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| 25. |
- Franzén, Stephanie, et al.
(författare)
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Intrarenal activation of endothelin type B receptors improves kidney oxygenation in type 1 diabetic rats
- 2018
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Ingår i: American Journal of Physiology - Renal Physiology. - : AMER PHYSIOLOGICAL SOC. - 1931-857X .- 1522-1466. ; 314:3, s. F439-F444
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Tidskriftsartikel (refereegranskat)abstract
- About one-third of patients with type 1 diabetes develops kidney disease. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease, including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. Endothelin type B receptors (ETB-R) can induce vasodilation of the renal vasculature and also regulate tubular sodium handling. However, the role of ETB-R in kidney oxygen homeostasis is unknown. The effects of acute intrarenal ETB-R activation (sarafotoxin 6c for 30-40 min; 0.78 pmol/h directly into the renal artery) on kidney function and oxygen metabolism were investigated in normoglycemic controls and insulinopenic male Sprague-Dawley rats administered streptozotocin (55 mg/kg) 2 wk before the acute experiments. Intrarenal activation of ETB-R improved oxygenation in the hypoxic diabetic kidney. However, the effects on diabetes-induced increased kidney oxygen consumption could not explain the improved oxygenation. Rather, the improved kidney oxygenation was due to hemodynamic effects increasing oxygen delivery without increasing glomerular filtration or tubular sodium load. In conclusion, increased ETB-R signaling in the diabetic kidney improves intrarenal tissue oxygenation due to increased oxygen delivery secondary to increased renal blood flow.
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| 26. |
- Friederich, Malou, 1983-, et al.
(författare)
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Deletion of Uncoupling Protein-2 reduces renal mitochondrial leak respiration, intrarenal hypoxia and proteinuria in a mouse model of type 1 diabetes
- 2018
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Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 223:4
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Tidskriftsartikel (refereegranskat)abstract
- AimUncoupling protein-2 (UCP-2) can induce mitochondrial uncoupling in the diabetic kidney. Although mitochondrial uncoupling reduces oxidative stress originating from the mitochondria and can be regarded as a protective mechanism, the increased oxygen consumption occurring secondarily to increased mitochondria uncoupling, that is leak respiration, may contribute to kidney tissue hypoxia. Using UCP-2(-/-) mice, we tested the hypothesis that UCP-2-mediated leak respiration is important for the development of diabetes-induced intrarenal hypoxia and proteinuria. MethodsKidney function, invivo oxygen metabolism, urinary protein leakage and mitochondrial function were determined in wild-type and UCP-2(-/-) mice during normoglycaemia and 2weeks after diabetes induction. ResultsDiabetic wild-type mice displayed mitochondrial leak respiration, pronounced intrarenal hypoxia, proteinuria and increased urinary KIM-1 excretion. However, diabetic UCP-2(-/-) mice did not develop increased mitochondrial leak respiration and presented with normal intrarenal oxygen levels, urinary protein and KIM-1 excretion. ConclusionAlthough functioning as an antioxidant system, mitochondria uncoupling is always in co-occurrence with increased oxygen consumption, that is leak respiration; a potentially detrimental side effect as it can result in kidney tissue hypoxia; an acknowledged unifying pathway to nephropathy. Indeed, this study demonstrates a novel mechanism in which UCP-2-mediated mitochondrial leak respiration is necessary for the development of diabetes-induced intrarenal tissue hypoxia and proteinuria.
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| 27. |
- Friederich, Malou, 1983-, et al.
(författare)
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Identification and distribution of uncoupling protein isoforms in the normal and diabetic rat kidney
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - New York : Springer. - 0065-2598 .- 2214-8019. - 9780387859972 ; 645, s. 205-212
-
Tidskriftsartikel (refereegranskat)abstract
- Uncoupling protein (UCP)-2 and -3 are ubiquitously expressed throughout the body but there is currently no information regarding the expression and distribution of the different UCP isoforms in the kidney. Due to the known cross-reactivity of the antibodies presently available for detection of UCP-2 and -3 proteins, we measured the mRNA expression of UCP-1, -2 and -3 in the rat kidney in order to detect the kidney-specific UCP isoforms. Thereafter, we determined the intrarenal distribution of the detected UCP isoforms using immunohistochemistry. Thereafter, we compared the protein levels in control and streptozotocin-induced diabetic rats using Western blot. Expressions of the UCP isoforms were also performed in brown adipose tissue and heart as positive controls for UCP-1 and 3, respectively. UCP-2 mRNA was the only isoform detected in the kidney. UCP-2 protein expression in the kidney cortex was localized to proximal tubular cells, but not glomerulus or distal nephron. In the medulla, UCP-2 was localized to cells of the medullary thick ascending loop of Henle, but not to the vasculature or parts of the nephron located in the inner medulla. Western blot showed that diabetic kidneys have about 2.5-fold higher UCP-2 levels compared to controls. In conclusion, UCP-2 is the only isoform detectable in the kidney and UCP-2 protein can be detected in proximal tubular cells and cells of the medullary thick ascending loop of Henle. Furthermore, diabetic rats have increased UCP-2 levels compared to controls, but the mechanisms underlying this increase and its consequences warrants further studies.
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| 28. |
- Friederich-Persson, Malou, et al.
(författare)
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Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage : effects of triiodothyronine and dinitrophenol in normoglycemic rats.
- 2013
-
Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer-Verlag New York. - 0065-2598 .- 2214-8019. - 9781461474111 - 9781461472568 ; 789, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.
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| 29. |
- Helle, Frank, et al.
(författare)
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Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C
- 2009
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 296:1, s. F78-F86
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Tidskriftsartikel (refereegranskat)abstract
- Two-kidney, one-clip (2K1C) is a model of renovascular hypertension where we previously found an exaggerated intracellular calcium (Ca(i)(2+)) response to ANG II in isolated afferent arterioles (AAs) from the clipped kidney (Helle F, Vagnes OB, Iversen BM. Am J Physiol Renal Physiol 291: F140-F147, 2006). To test whether nitric oxide (NO) ameliorates the exaggerated ANG II response in 2K1C, we studied ANG II (10(-7) mol/l)-induced calcium signaling and contractility with or without the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME). In AAs from the nonclipped kidney, l-NAME increased the ANG II-induced Ca(i)(2+) response from 0.28 +/- 0.05 to 0.55 +/- 0.09 (fura 2, 340 nm/380 nm ratio) and increased contraction from 80 +/- 6 to 60 +/- 6% of baseline (P < 0.05). In vessels from sham and clipped kidneys, l-NAME had no effect. In diaminofluorescein-FM diacetate-loaded AAs from the nonclipped kidney, ANG II increased NO-derived fluorescence to 145 +/- 34% of baseline (P < 0.05 vs. sham), but not in vessels from the sham or clipped kidney. Endothelial NOS (eNOS) mRNA and ser-1177 phosphorylation were unchanged in both kidneys from 2K1C, while eNOS protein was reduced in the clipped kidney compared with sham. Cationic amino acid transferase-1 and 2 mRNAs were increased in 2K1C, indicating increased availability of l-arginine for NO synthesis, but counteracted by decreased scavenging of the eNOS inhibitor asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolase 2. In conclusion, the Ca(i)(2+) and contractile responses to ANG II are blunted by NO release in the nonclipped kidney. This may protect the nonclipped kidney from the hypertension and elevated ANG II levels in 2K1C.
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| 30. |
- Holmberg, Tora, 1967-, et al.
(författare)
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Introduction : Why death matters
- 2019
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Ingår i: Death matters. - Cham, Switzerland : Palgrave Macmillan. - 9783030114848 ; , s. 1-21
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Bokkapitel (refereegranskat)
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| 31. |
- Juul, Troels, et al.
(författare)
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Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells : A novel technique for cell energy phenotyping.
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 78:2, s. 457-461
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: It has been demonstrated that hyperpolarized (13) C MR is a useful tool to study cultured cells. However, cells in culture can alter phenotype, which raises concerns regarding the in vivo significance of such findings. Here we investigate if metabolic phenotyping using hyperpolarized (13) C MR is suitable for cells isolated from kidney tissue, without prior cell culture.METHODS: Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system.RESULTS: Isolation of tubular cells from less than 2 g of kidney tissue generally resulted in more than 10 million live tubular cells. This amount of cells was enough to yield robust signals from the conversion of (13) C-pyruvate to lactate, bicarbonate and alanine, demonstrating that metabolic flux by means of both anaerobic and aerobic pathways can be quantified using this technique.CONCLUSION: Ex vivo metabolic phenotyping using hyperpolarized (13) C MR in a preclinical system is a useful technique to study energy metabolism in freshly isolated renal tubular cells. This technique has the potential to advance our understanding of both normal cell physiology as well as pathological processes contributing to kidney disease.
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| 32. |
- Lai, En Yin, et al.
(författare)
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Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass
- 2012
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 303:1, s. F64-74
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that reactive oxygen species (ROS) contributed to renal hypoxia in C57BL/6 mice with ⅚ surgical reduction of renal mass (RRM). ROS can activate the mitochondrial uncoupling protein 2 (UCP-2) and increase O(2) usage. However, UCP-2 can be inactivated by glutathionylation. Mice were fed normal (NS)- or high-salt (HS) diets, and HS mice received the antioxidant drug tempol or vehicle for 3 mo. Since salt intake did not affect the tubular Na(+) transport per O(2) consumed (T(Na/)Q(O2)), further studies were confined to HS mice. RRM mice had increased excretion of 8-isoprostane F(2α) and H(2)O(2), renal expression of UCP-2 and renal O(2) extraction, and reduced T(Na/)Q(O2) (sham: 20 ± 2 vs. RRM: 10 ± 1 μmol/μmol; P < 0.05) and cortical Po(2) (sham: 43 ± 2, RRM: 29 ± 2 mmHg; P < 0.02). Tempol normalized all these parameters while further increasing compensatory renal growth and glomerular volume. RRM mice had preserved blood pressure, glomeruli, and patchy tubulointerstitial fibrosis. The patterns of protein expression in the renal cortex suggested that RRM kidneys had increased ROS from upregulated p22(phox), NOX-2, and -4 and that ROS-dependent increases in UCP-2 led to hypoxia that activated transforming growth factor-β whereas erythroid-related factor 2 (Nrf-2), glutathione peroxidase-1, and glutathione-S-transferase mu-1 were upregulated independently of ROS. We conclude that RRM activated distinct processes: a ROS-dependent activation of UCP-2 leading to inefficient renal O(2) usage and cortical hypoxia that was offset by Nrf-2-dependent glutathionylation. Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2.
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| 33. |
- Laustsen, Christoffer, et al.
(författare)
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Antioxidant treatment attenuates lactate production in diabetic nephropathy
- 2017
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 312:1, s. F192-F199
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Tidskriftsartikel (refereegranskat)abstract
- The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned (13)C/(1)H-volume rat coil. The rats received intravenous hyperpolarized [1-(13)C]pyruvate and were imaged using a slice-selective (13)C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [(13)C]alanine levels, indicating an intact glucose-alanine cycle, or [(13)C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes.
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| 34. |
- Laustsen, Christoffer, et al.
(författare)
-
High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes
- 2019
-
Ingår i: Tomography. - : GRAPHO PUBLICATIONS. - 2379-1381 .- 2379-139X. ; 5:2, s. 239-247
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Tidskriftsartikel (refereegranskat)abstract
- Intrarenal hypoxia develops within a few days after the onset of insulinopenic diabetes in an experimental animal model (ie, a model of type-1 diabetes). Although diabetes-induced hypoxia results in increased renal lactate formation, mitochondrial function is well maintained, a condition commonly referred to as pseudohypoxia. However, the metabolic effects of significantly elevated lactate levels remain unclear. We therefore investigated in diabetic animals the response to acute intrarenal hypoxia in the presence of high renal lactate formation to delineate mechanistic pathways and compare these findings to healthy control animals. Hyperpolarized C-13-MRI and blood oxygenation level-dependent 1H-MRI was used to investigate the renal metabolism of [1-C-13] pyruvate and oxygenation following acutely altered oxygen content in the breathing gas in a streptozotocin rat model of type-1 diabetes with and without insulin treatment and compared with healthy control rats. The lactate signal in the diabetic kidney was reduced by 12%-16% during hypoxia in diabetic rats irrespective of insulin supplementation. In contrast, healthy controls displayed the well-known Pasteur effect manifested as a 10% increased lactate signal following reduction of oxygen in the inspired air. Reduced expression of the monocarboxyl transporter-4 may account for altered response to hypoxia in diabetes with a high intrarenal pyruvate-to-lactate conversion. Reduced intrarenal lactate formation in response to hypoxia in diabetes shows the existence of a different metabolic phenotype, which is independent of insulin, as insulin supplementation was unable to affect the pyruvate-to-lactate conversion in the diabetic kidney.
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| 35. |
- Laustsen, Christoffer, et al.
(författare)
-
Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney
- 2014
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:12
-
Tidskriftsartikel (refereegranskat)abstract
- Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.
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| 36. |
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| 37. |
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| 38. |
- Luther, Tomas, et al.
(författare)
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Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging : a prospective case control study
- 2022
-
Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
-
Tidskriftsartikel (refereegranskat)abstract
- Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data support this. In this prospective case-control study we aimed to investigate differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging (mpMRI) in critically ill COVID-19 patients with and without AKI. Nineteen patients without prior kidney disease treated in intensive care for respiratory failure were examined. Ten patients had AKI and nine patients did not have AKI using Kidney Disease: Improving Global Outcomes Creatinine criteria. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423-753] vs. 859 [746-920] ml/min, P = 0.037). Regional perfusion was reduced in both cortex (76 [51-112] vs. 146 [123-169] mL/100g/min, P = 0.015) and medulla (28 [18-47] vs. 47 [38-73] mL/100g/min, P = 0.03). Renal venous saturation was similar in both groups (72% [64-75] vs. 72% [63-84], ns.), as was regional oxygenation (R2*) in cortex (17 [16-19] vs. 17 [16-18] 1/s, ns.) and medulla (29 [24-39] vs. 27 [23-29] 1/s, ns.). We conclude that in critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flow are reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting.
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| 39. |
- Luther, Tomas, et al.
(författare)
-
Plasma expansion and renal perfusion in critical COVID-19 with AKI: a prospective case control study
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 have previously been demonstrated. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in critically ill patients with AKI compared to similar patients without AKI. Methods: A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5ml/kg Ringer’s Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Results: Nine patients with AKI and eight without were included in the study. The hemodynamic response to plasma expansion was similar in both groups with increases in MAP by 18 mmHg (CI 8-28) and 20 mmHg (CI 10-31) in patients with and without AKI respectively. Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion in either group. There were however there was a reduction of medullary perfusion in patients without AKI from 55 (CI 39-79) to 34 (CI 24-48) ml/min/100g (P = 0.0027).Conclusion: Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19.
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| 40. |
- Luther, Tomas, et al.
(författare)
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Renal mitochondrial dysfunction in ovine experimental sepsis-associated acute kidney injury
- 2023
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 324:6, s. 571-580
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Tidskriftsartikel (refereegranskat)abstract
- Sheep develop sepsis-associated acute kidney injury (SA-AKI) during experimental sepsis despite normal to increased renal oxygen delivery. A disturbed relation between oxygen consumption (V_ O2) and renal Na thorn transport has been demonstrated in sheep and in clinical studies of AKI, which could be explained by mitochondrial dysfunction. We investigated the function of isolated renal mitochondria compared with renal oxygen handling in an ovine hyperdynamic model of SA-AKI. Anesthetized sheep were randomized to either an infusion of live Escherichia coli with resuscitative measures (sepsis group; n = 13 animals) or served as controls (n = 8 animals) for 28 h. Renal V_ O2 and Na thorn transport were repeatedly measured. Live cortical mitochondria were isolated at baseline and at the end of the experiment and assessed in vitro with high-resolution respirometry. Sepsis markedly reduced creatinine clearance, and the relation between Na thorn transport and renal V_ O2 was decreased in septic sheep compared with control sheep. Cortical mitochondrial function was altered in septic sheep with a reduced respiratory control ratio (6.0 & PLUSMN; 1.5 vs. 8.2 & PLUSMN; 1.6, P = 0.006) and increased complex II-to-complex I ratio during state 3 (1.6 & PLUSMN; 0.2 vs. 1.3 & PLUSMN; 0.1, P = 0.0014) mainly due to decreased complex I-dependent state 3 respiration (P = 0.016). However, no differences in renal mitochondrial efficiency or mitochondrial uncoupling were found. In conclusion, renal mitochondrial dysfunction composed of a reduction of the respiratory control ratio and an increased complex II/complex I relation in state 3 was demonstrated in an ovine model of SA-AKI. However, the disturbed relation between renal V_ O2 and renal Na thorn transport could not be explained by a change in renal cortical mitochondrial efficiency or uncoupling.NEW & NOTEWORTHY We studied the function of renal cortical mitochondria in relation to oxygen consumption in an ovine model of sepsis with acute kidney injury. We demonstrated changes in the electron transport chain induced by sepsis consisting of a reduced respiratory control ratio mainly by a reduced complex I-mediated respiration. Neither an increase in mitochondrial uncoupling nor a reduction in mitochondrial efficiency was demonstrated and cannot explain why oxygen consumption was unaffected despite reduced tubular transport.
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| 41. |
- Melican, K, et al.
(författare)
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Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis
- 2008
-
Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 10:10, s. 1987-1998
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Tidskriftsartikel (refereegranskat)abstract
- Ascending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy to investigate the crucial early phases of uropathogenic Escherichia coli induced pyelonephritis within a living animal. Our results reveal a previously undescribed innate vascular response to mucosal infection, allowing isolation and eradication of the pathogen. The extremely rapid host response to mucosal infection was highlighted by the triggering of a cascade of events within 3-4 h. Epithelial signalling produced an increase in cellular O-2 consumption and affected microvascular flow by clotting, causing localized ischaemia. Subsequent ischaemic damage affected pathophysiology with actin re-arrangement and epithelial sloughing leading to paracellular bacterial movement. A denuded tubular basement membrane is shown to hinder immediate dissemination of bacteria, giving the host time to isolate the infection by clotting. Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis.
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| 42. |
- Mähler, Roger, 1965-, et al.
(författare)
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Implementing and sustaining a DH infrastructur : The HUMlab experience
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- To curate processes within the digital humanities, an elaborate infrastructure of technology, supporting processes, physical spaces, competences, and human attitudes is needed, which can be challenging to create and sustain in the academia of humanities. In this poster we will share our experiences, good as well as bad, and how we have tackled the challenges of working within the digital humanities.The physical spaces of HUMlab are open and accessible, where technicians, students, and researchers from a wide variety of fields can meet and collaborate. The spaces in HUMlab have been designed with the aim of creating an appealing and attractive ‘meeting place’ with a technological infrastructure that breaks interdisciplinary barriers. The codesign of digital research methodologies and tools also functions across the disciplines and joins knowledge from different fields.The supporting processes, and the way they are executed, emphasise collaboration, knowledge sharing, and joint venture. The project model used in software development is based on an agile approach that has been adapted to the special needs and demands of academia and research within the humanities. Supporting workflows have been specified and implemented (e.g., stakeholder discussion, project initialization) with tollgates and templates. The real challenge is to create formalized workflows that promote new ideas, quality, creativity, innovation, and individual development.An open mindset is required to achieve and sustain interdisciplinarity and collaboration on equal terms. The working process must allow mistakes and encourage new ideas. Part of the challenge is to build trust and share knowledge in a dialogue that translates scholarly needs with technology to give added values.Technology plays an important part of HUMlab (e.g., a multitude of screen scapes), but even more important is the critical attitude towards the technology and how it is used. It is vital to understand the underlying epistemology of different technologies, and the methods and tools, and to have transparency on how they are applied in order to achieve certain (research) objectives.A real challenge is to sustain the numerous competences needed within the fields of digital humanities and humanities computing (especially when you don’t know the needs of the next collaboration). At HUMlab, this is done by so-called pet projects (freedom to work with personal projects), focus projects (small projects to expand knowledge in certain areas, and to step out of your ‘comfort zone’), assigned fields of interest (personal responsibility to sustain knowledge for a specific fields), and a competence matrix at an organizational level that is based on HUMlab’s needs and vision for the future, but also dynamic and flexible and adapting to an ever-changing world.
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| 43. |
- Nensén, Oskar, 1992-
(författare)
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Intrarenal oxygen homeostasis in acute and chronic kidney disease
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Renal hypoxia has been recognized as a common feature of acute and chronic kidney injury arising from varying etiologies. It has also been proposed to provide a driving mechanism for the transition from acute to chronic kidney disease (CKD). Acute kidney injury (AKI) is common in the critically ill patient, but no targeted therapies exist to treat and prevent kidney injury and the progression to chronic kidney injury. This thesis aims to describe the alterations in renal hemodynamics and oxygenation in the setting of acute and chronic kidney injury and elucidate if restoration of the oxygen supply/demand relationship can prevent kidney dysfunction in these settings. Disruption of the filtration barrier and back-leak of sodium into the proximal tubule, resulting in a futile transport cycle, has been proposed to provide an explanation for the disruption of the oxygen supply/demand relationship in AKI. By inhibiting proximal sodium transport using the drug acetazolamide in an ischemia reperfusion (IR) model of AKI in rats, sodium transport efficiency and glomerular filtration rate (GFR) were further impaired. This demonstrates that proximal tubular function is critical in the recovery from AKI. Hypoxia has been previously demonstrated to cause nephropathy. In a rat model of IR associated AKI we were able to demonstrate that further impairing renal oxygenation by subjecting rats to systemic hypoxia via alterations of inspired oxygen content. Conversely, by increasing the fraction of inspired oxygen and increasing renal oxygen tension kidney dysfunction could be prevented. This provides support for the theory that increasing renal oxygenation can ameliorate AKI. Diabetes is a leading cause of CKD and associated with renal hypoxia, especially in the real medulla. The diuretic furosemide inhibits sodium transport in the outer medulla and has previously been demonstrated to increase tissue oxygen tension in this region. However, the hemodynamic actions of furosemide on the kidney are still unclear. By administering furosemide to diabetic rats with intact and removed renal capsule we could show that the reduction in renal blood flow through increased vascular resistance was due to increased hydrostatic pressure and removing the renal capsule completely ameliorated the reduction in renal blood flow. Major haemorrhage is a clinically relevant cause of AKI. In a rat model of haemorrhage associated AKI, loss of kidney function was prevented by treatment with OR-1896, an active metabolite of levosimendan. OR-1896 restored renal oxygenation by increasing renal blood flow through reduced renal vascular resistance and completely ameliorated the reduction in GFR observed in untreated haemorrhaged animals. In summary, the results from the studies included in this thesis show that preventing renal hypoxia and restoring renal oxygenation has the potential to prevent loss of function in kidney disease.
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| 44. |
- Nensén, Oskar, et al.
(författare)
-
Intrarenal oxygenation determines kidney function during the recovery from an ischemic insult
- 2020
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 319:6, s. F1067-F1072
-
Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery, and intrarenal hypoxia is a hallmark of AKI and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in the recovery from an ischemic insult is presently unclear. The present study was designed to investigate 1) the role of systemic hypoxia in the acute progression and recovery of AKI and 2) whether increased intrarenal oxygenation improves recovery from an ischemic insult. Anesthetized male Sprague-Dawley rats were subjected to unilateral warm renal ischemia for 45 min followed by 2 h of reperfusion under systemic hypoxia (10% inspired oxygen), normoxia (21% inspired oxygen), or hyperoxia (60% inspired oxygen). Intrarenal oxygen tension was successfully manipulated by altering the inspired oxygen. Glomerular filtration rate (GFR) before the ischemic insult was independent of intrarenal oxygen tension. GFR during the recovery from the ischemic insult was significantly lower compared with baseline in all groups (3 ± 1%, 13 ± 1%, and 30 ± 11% of baseline for hypoxia, normoxia, and hyperoxia, respectively). However, GFR was significantly higher in hyperoxia than hypoxia (P < 0.05, hypoxia vs. hyperoxia). During recovery, renal blood flow was only reduced in hyperoxia, as a consequence of increased renal vascular resistance. In conclusion, the present study demonstrates that renal function during the recovery from an ischemic insult is dependent on intrarenal oxygen availability, and normobaric hyperoxia treatment has the potential to protect kidney function.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Nensén, Oskar, et al.
(författare)
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Role of carbonic anhydrase in acute recovery following renal ischemia reperfusion injury
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia reperfusion (IR) injury can cause acute kidney injury. It has previously been reported that kidney oxygen consumption (QO(2)) in relation to glomerular filtration rate (GFR), and thus tubular sodium load, is markedly increased following IR injury, indicating reduced electrolyte transport efficiency. Since proximal tubular sodium reabsorption (TNa) is a major contributor to overall kidney QO(2), we investigated whether inhibition of proximal tubular sodium transport through carbonic anhydrase (CA) inhibition would improve renal oxygenation following ischemia reperfusion. Anesthetized adult male Sprague Dawley rats were administered the CA inhibitor acetazolamide (50 mg/kg bolus iv), or volume-matched vehicle, and kidney function, hemodynamics and QO(2) were estimated before and after 45 minutes of unilateral complete warm renal ischemia. CA inhibition per se reduced GFR (-20%) and TNa (-22%), while it increased urine flow and urinary sodium excretion (36-fold). Renal blood flow was reduced (-31%) due to increased renal vascular resistance (+37%) without affecting QO(2). IR per se resulted in similar decrease in GFR and TNa, independently of CA activity. However, the QO(2)/TNa ratio following ischemia-reperfusion was profoundly increased in the group receiving CA inhibition, indicating a significant contribution of basal oxygen metabolism to the total kidney QO(2) following inhibition of proximal tubular function after IR injury. Ischemia increased urinary excretion of kidney injury molecule-1, an effect that was unaffected by CA. In conclusion, this study demonstrates that CA inhibition further impairs renal oxygenation and does not protect tubular function in the acute phase following IR injury. Furthermore, these results indicate a major role of the proximal tubule in the acute recovery from an ischemic insult.
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- Nordquist, Lina, 1977-, et al.
(författare)
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Diabetes-induced alterations in renal medullary microcirculation and metabolism
- 2007
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Ingår i: Current diabetes reviews. - 1573-3998. ; 3:1, s. 53-65
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Forskningsöversikt (refereegranskat)abstract
- Diabetes-induced renal complications, i.e. diabetes nephropathy, are a major cause of morbidity and mortality. The exact mechanisms mediating the negative influence of hyperglycemia on renal function are unclear, although several hypotheses have been postulated. Cellular mechanisms include glucose-induced excessive formation of reactive oxygen species, increased glucose flux through polyol pathway and pentose phosphate shunt, formation of advanced glycation end-products and activation of protein kinase C and NADPH oxidase. However, the renal effects in vivo of each and every one of these mechanisms are less clear, although recent studies have shown several major alterations predominantly in the renal medulla as a result of sustained hyperglycemia. Already during normal conditions, the renal medulla has a remarkably low oxygen tension (PO2) and a high degree of non-oxygen dependent energy metabolism. Alterations in either blood perfusion or oxygen delivery to the medullary region will have significant effects on both regional metabolism and total kidney function. Recently, sustained hyperglycemia has been shown to induce a pronounced reduction in preferentially renal medullary PO2. This review will present the current knowledge of diabetes-induced alterations in renal medullary metabolism and function, but also discuss future targets for prevention of diabetic nephropathy.
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