| 1. |
- Berglund, Felix, et al.
(författare)
-
Acute and long-term renal effects after iodine contrast media-enhanced computerised tomography in the critically ill-a retrospective bi-centre cohort study.
- 2024
-
Ingår i: European Radiology. - 0938-7994 .- 1432-1084. ; 34:3, s. 1736-1745
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care.METHODS: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function.RESULTS: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543).CONCLUSIONS: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units.CLINICAL RELEVANCE STATEMENT: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT.KEY POINTS: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contrast media did not have an increased incidence of acute kidney injury or persistent decline in renal function. • A more clearly defined risk of iodine contrast media helps guide clinical decisions whether to perform contrast-enhanced CTs or not.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Andersson, Magnus, et al.
(författare)
-
How cultural values are reflected on the housing market : direct effects and the cultural spillover
- 2019
-
Ingår i: International Journal of Housing Markets and Analysis. - : Emerald Group Publishing Limited. - 1753-8270 .- 1753-8289. ; 12:3, s. 405-423
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this paper is to analyse two questions. First, is there, and if so, how large is the price premium paid for a building exhibiting a cultural value? Second, are there any spillover effects of buildings with cultural values on sales prices of neighbouring houses? Design/methodology/approach: Using a unique database of all buildings in the region of Halland, Sweden, combined with transaction data, hedonic models can be estimated, with spatially lagged variables describing proximity to three classes of culturally classified building – A, B and C – corresponding to building of national interest, building of regional interest and building of local interest. In addition, the authors also estimate models with a spatial specification on the error term, in an attempt to control for omitted variables. Findings: The results indicate that cultural classification plays a role in determining the price of a property, with large effects (ranging between 36 and 60% price premiums) for the highest classification. In addition, the authors find evidence of a cultural externality, houses in the vicinity of building with high cultural value sell at a small, but statistically significant premium of 1%. Originality/value: The cultural externality may be overlooked when it comes to valuation of cultural values in society, and therefore, it is likely that warranted protection acts to preserve cultural values in buildings become less than the social optimum. This paper suggests a new measure to cultural values contrasting previous research that rely on cultural preservation. This approach should limit problems with measurement errors that may lead to biased results.
|
|
| 5. |
- Backman, Fredrik
(författare)
-
Energy efficiency in Swedish SMEs : Exploring barriers, knowledge creation and the role of municipal energy efficiency programs
- 2018
-
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.
|
|
| 6. |
- Barbu, Andreea, et al.
(författare)
-
The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets
- 2015
-
Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 97, s. 124-129
-
Tidskriftsartikel (refereegranskat)abstract
- The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.
|
|
| 7. |
- Berg, Christoffer, 1986-
(författare)
-
Public Planning, Neoliberal Hybridity and Local Activism in Sundbyberg : Epochal Reconfiguration of Urban Development in Greater Stockholm
- 2022
-
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.
|
|
| 8. |
- Bergman, Hilde-Marlene, et al.
(författare)
-
Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
- 2019
-
Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 411:13, s. 2809-2816
-
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.
|
|
| 9. |
- Berntson, Lillemor, 1957-, et al.
(författare)
-
Haptoglobin in Juvenile Idiopathic Arthritis
- 2022
-
Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.METHODS: Plasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).RESULTS: At 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).CONCLUSION: Hp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.
|
|
| 10. |
- Buckland, Philip I., et al.
(författare)
-
Integrating human dimensions of Arctic palaeoenvironmental science : SEAD – the strategic environmental archaeology database
- 2011
-
Ingår i: Journal of Archaeological Science. - : Elsevier. - 0305-4403 .- 1095-9238. ; 38:2, s. 345-351
-
Tidskriftsartikel (refereegranskat)abstract
- Environmental change has a human dimension, and has had so for at least the last 10 000 years. The prehistoric impact of people on the Arctic landscape has occasionally left visible traces, such as house and field structures. More often than not, however, the only evidence available is at the microscopic or geochemical level, such as fossil insect and seed assemblages or changes in the physical and chemical properties of soils and sediments. These records are the subject of SEAD, a multidisciplinary database and software project currently underway at Umeå University, Sweden, which aims to create an online database and set of tools for investigating these traces, as part of an international research infrastructure for palaeoecology and environmental archaeology.
|
|
| 11. |
|
|
| 12. |
- Buckland, Philip I., 1973-, et al.
(författare)
-
The Strategic Environmental Archaeology Database : a resource for international, multiproxy and transdisciplinary studies of environmental and climatic change
- 2015
-
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).
|
|
| 13. |
- Bulut, Mehmet Börühan, 1987-
(författare)
-
Building as active elements of energy systems
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Buildings account for approximately 40% of the energy demand and 33% of the total greenhouse gas emissions in the European Union. Accordingly, there are several efforts that target energy efficiency in buildings both at the European and Swedish levels. The role of buildings in climate change mitigation, however, is not limited to energy savings. Buildings are expected to become key elements of the future smart energy systems by supplying and using energy in a more flexible way. Reducing the energy demand in buildings effectively and shifting the role of buildings in energy systems from ‘passive’ consumers to ‘active’ prosumers, however, require close interaction and cooperation between the energy and buildings sectors.Based on the data collected from interviews and a web survey, this doctoral thesis investigates the relationship between the energy and buildings sectors in Sweden at the inter-company level, presents key stakeholder views on smart energy features in buildings and investigates the opportunities and barriers for their adoption in Sweden and Hong Kong.The results of this thesis suggest a potential for improving the cooperation between the Swedish energy and buildings sectors, which was identified to be influenced by the following factors: district heating monopolies; energy efficiency efforts in the buildings sector; unsuccessful technology-neutrality of the building regulations; self-generation systems in buildings; and energy use patterns. Shifting the focus from self-gains to mutual gains appears crucial to strengthen the inter-sectoral cooperation, as there are several opportunities for achieving mutually beneficial solutions for the two sectors. This would, however, require significant changes in current practices and business models as well as the introduction of new technologies, which would allow for a more flexible energy supply and use. Accordingly, technologies that target flexible energy use in buildings are considered the most important smart energy features in buildings. The current high costs of technologies, such as home automation and smart electrical appliances, however, create the strongest barrier to adoption. Therefore, the introduction of new business and ownership models and the elimination of the institutional and regulatory barriers are crucial to achieve a wide-scale development of smart energy features in buildings. The results from Hong Kong suggest that institutional and regulatory barriers can particularly create strong hinders to the adoption of technologies.It is possible to achieve more sustainable energy systems, where buildings are active elements of networks that supply and use energy in a more flexible and ‘smarter’ way. Cooperation between the energy and buildings sectors can play a key role in the adoption of smart energy features in buildings and pave the way for the smart built environment of the future.
|
|
| 14. |
- Burden, Håkan, et al.
(författare)
-
Självkörande landsbygd
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Hur skulle autonoma fordon kunna användas inom kollektivtrafiken på landsbygden? Genom intervjuer, workshops och en RFI (request for information, ett första steg mot upphandling) har vi undersökt frågan utifrån fyra konkreta områden i Sverige – Lund, Gotland, Eskilstuna och Skellefteå. Med en definition av landsbygd baserad på individens mobilitet har vi sett att Sveriges landsbygd rymmer mindre orter på väg att avfolkas där äldre, barn och de utan körkort hade kunnat få bättre tillgång till samhällelig service med autonoma fordon. Vi har också sett att flera av landets nya arbetsplatser kommer befinna sig på landsbygden och därmed skapa ett mobilitetsbehov från staden till landet. För att kunna realisera de identifierade möjligheterna finns ett behov av att framföra fordonen i högre hastigheter samt att de ska kunna hantera mer komplexa trafiksituationer än vad dagens piloter i städerna visat. På landsbygden finns alltså ett utrymme för nya fordon att visa upp sig. Samtidigt ser vi hur man inte ska förvänta sig att investeringarna i autonoma fordon kommer betala sig på en linje, snarare behöver man lyfta blicken och se systemeffekten när stomlinjetrafiken blir mer attraktiv då bussarna går raka vägen istället för via mindre samhällen. Vi har inte sett några belägg på att den digitala infrastrukturen behöver utvecklas för att möjliggöra försök med autonoma fordon på någon av de undersökta rutterna. Dagens 4G-täckning är fullgod och fordonen borde ha tillgång till tillräckligt bra positioneringsdata för att bedriva verksamheten. Däremot ställs flera frågor om hur ersättningstrafiken organiseras när fordonen inte klarar av vädret, vem som står för säkrare hållplatser och hur chaufförens övriga ansvar realiseras när fordonet är förarlöst.
|
|
| 15. |
- Burmakin, Mikhail, et al.
(författare)
-
Pharmacological HIF-PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
- 2021
-
Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 233:1
-
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.
|
|
| 16. |
- Carlsson, Per-Ola, et al.
(författare)
-
Chronically decreased oxygen tension in rat pancreatic islets transplantedunder the kidney capsule
- 2000
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 69:5, s. 761-766
-
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.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Carlström, Eric, 1957, et al.
(författare)
-
Medical Emergencies During a Half Marathon Race - The Influence of Weather
- 2019
-
Ingår i: International Journal of Sports Medicine. - Stuttgart : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 40:5, s. 312-316
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to analyze the influence of weather conditions on medical emergencies in a half-marathon, specifically by evaluating its relation to the number of non-finishers, ambulance-required assistances, and collapses in need of ambulance as well as looking at the location of such emergencies on the race course. Seven years of data from the world's largest half marathon were used. Meteorological data were obtained from a nearby weather station, and the Physiological Equivalent Temperature (PET) index was used as a measure of general weather conditions. Of the 315,919 race starters, 104 runners out of the 140 ambulance-required assistances needed ambulance services due to collapses. Maximum air temperature and PET significantly co-variated with ambulance-required assistances, collapses, and non-finishers (R (2) =0.65-0.92; p=0.001-0.03). When air temperatures vary between 15-29 degrees C, an increase of 1 degrees C results in an increase of 2.5 (0.008/1000) ambulance-required assistances, 2.5 (0.008/1000) collapses (needing ambulance services), and 107 (0.34/1000) non-finishers. The results also indicate that when the daily maximum PET varies between 18-35 degrees C, an increase of 1 degrees C PET results in an increase of 1.8 collapses (0.006/1000) needing ambulance services and 66 non-finishers (0.21/1000).
|
|
| 25. |
- Carlström, Mattias, et al.
(författare)
-
Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals
- 2008
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 294:2, s. 362-370
-
Tidskriftsartikel (refereegranskat)abstract
- Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N-G- nitro-L-arginine methyl ester (L-NAME) or L-arginine. Blood samples for ADMA, SDMA, and L-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or L-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to L-NAME was attenuated and L-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. L-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Carvalho, Carla, 1988-
(författare)
-
The Role of Kidney Oxygen Homeostasis for the Development of Kidney Disease
- 2019
-
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.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Christensen, Michael, et al.
(författare)
-
Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein-2
- 2019
-
Ingår i: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 35:2
-
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.
|
|
| 32. |
|
|
| 33. |
- Davids, Mariska, et al.
(författare)
-
Simultaneous determination of asymmetric and symmetric dimethylarginine, L-monomethylarginine, L-arginine, and L-homoarginine in biological samples using stable isotope dilution liquid chromatography tandem mass spectrometry
- 2012
-
Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 900, s. 38-47
-
Tidskriftsartikel (refereegranskat)abstract
- Production of the endogenous vasodilator nitric oxide (NO) from L-arginine by NO synthase is modulated by L-homoarginine, L-monomethylargine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Here we report on a stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of these metabolites in plasma, cells and tissues. After addition of the internal standards (D-7-ADMA, D-4-L-homoarginine and C-13(6)-Larginine), analytes were extracted from the samples using Waters Oasis MCX solid phase extraction cartridges. Butylated analytes were separated isocratically on a Waters XTerra MS C18 column (3.5 mu m. 3.9 mm x 100 mm) using 600 mg/L ammonium formate in water - acetonitrile (95.5:4.5, v/v) containing 0.1 vol% formic acid, and subsequently measured on an AB Sciex API 3000 triple quadrupole mass spectrometer. Multiple reaction monitoring in positive mode was used for analyte quantification. Validation was performed in plasma. Calibration lines were linear (r(2) >= 0.9979) and lower limits of quantification in plasma were 0.4 nM for ADMA and SDMA and 0.8 nM for the other analytes. Accuracy (% bias) was <3% except for MMA (<7%), intra-assay precision (expressed as CV) was <3.5%, inter-assay precision <9.6%, and recovery 92.9-103.2% for all analytes. The method showed good correlation (r(2) >= 0.9125) with our previously validated HPLC-fluorescence method for measurement in plasma, and was implemented with good performance for measurement of tissue samples. Application of the method revealed the remarkably fast (i.e. within 60 min) appearance in plasma of stable isotope-labeled ADMA, SDMA, and MMA during infusion of D-3-methyl-1-C-13-methionine in healthy volunteers.
|
|
| 34. |
-
Death Matters : Cultural Sociology of Mortal Life
- 2019
-
Samlingsverk (redaktörskap) (refereegranskat)abstract
- This book investigates death as part of contemporary everyday experience and practices. Through a cultural sociological lens, it studies death as it remains constantly at the edge of our consciousness, shaping the ways in which we move through social reality. As such, Death Matters is a significant contribution to death studies, going beyond traditional parameters of the field by addressing the cultural omnipresence of death.The contributions analyses several death-related meaning-making processes, arguing that meanings emerging from culturally shared narratives, social institutions, and material conditions, are just as important as ’death practices’ in understanding the role of death in society. Drawing on the related themes of places of absence and presence, disease and bodies, and persons and non-persons, the authors explore a variety of areas of social life, from haunting to celebrity deaths, to move the notion of death from the margins of social reality to on going everyday life.
|
|
| 35. |
- Eckerbom, Per, 1974-
(författare)
-
Assessment of Renal Physiology Using Functional MRI
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Kidney injury is a major cause of morbidity and mortality throughout the world, leading to substantial individual suffering and to a heavy financial burden for the society. A large number of common conditions such as diabetes, hypertension, autoimmune diseases and infections are highly associated with kidney injury. Disturbances in renal perfusion and oxygenation are believed to be involved in the pathogenesis of kidney injury and are therefore of interest to investigate closely. Studies to further the understanding of kidney injury have previously most often involved invasive procedures or ionizing radiation which have limited studies in humans due to ethical reasons. Hence there is a need to explore and implement noninvasive, nonionizing techniques to carry out human studies of renal physiology in health and disease. This thesis aimed to do so using a number of novel, noninvasive magnetic resonance imaging (MRI) techniques. In the first study of this thesis, we scanned the kidneys of healthy volunteers with noninvasive MRI and found significant differences between the renal cortex, inner and outer medulla regarding blood flow, oxygenation, water diffusion and tissue characteristics. In the second study we scanned the kidneys with MRI and collected urine from healthy volunteers every fourth hour for 24 hours and found circadian variations for total renal blood flow as well as for a number of urinary parameters. Renal oxygenation was stable with only small diurnal variations. In the third study we implemented the MRI techniques used in study 1 and 2 and one additional MRI technique in COVID-19 patients admitted to the intensive care unit for severe respiratory failure, with and without acute kidney injury (AKI). We found significantly reduced total renal blood flow as well as cortical and medullary perfusion in patients with AKI compared to patients without AKI. No significant difference was found between the two groups regarding renal oxygenation, water diffusion or tissue characteristics. In the fourth study we used the same MRI techniques as in study 3 to follow up patients previously treated for severe COVID-19 without and with different degrees of AKI. We found significantly reduced apparent diffusion coefficient (ADC) and total renal blood flow in patients that had high grade AKI compared to patients that did not have AKI during hospitalization for COVID-19. No significant difference regarding oxygenation was found between the groups.In conclusion, this thesis shows that it is possible to use multiparametric noninvasive MRI for renal studies in clinical practice.
|
|
| 36. |
- Eckerbom, Per, 1974-, et al.
(författare)
-
Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging
- 2020
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 319:6, s. F966-F978
-
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.
|
|
| 37. |
- Eckerbom, Per, 1974-, et al.
(författare)
-
Intravoxel Incoherent Motion MR Imaging of the Kidney : Pilot Study
- 2013
-
Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598 .- 2214-8019. ; 765, s. 55-58
-
Tidskriftsartikel (refereegranskat)abstract
- MR examinations (Achieva 3 T, Philips, Best, The Netherlands) were performed at five different occasions in a healthy volunteer (male 60 years) and in one renal cancer patient (male 78 years) with normal renal function (creatinine 88 μmol/L). Intravoxel incoherent motion (IVIM) coefficients D + D* were measured using respiratory-triggered diffusion-weighted spin-echo echo-planar imaging. Perfusion data of the patient were acquired using a saturation-recovery gradient-echo sequence and with the bolus of Gd-BOPTA (Multihance). D + D* were computed by monoexponential fitting of MR signal intensity attenuation versus b for b = 0, 50, 100, 150 s/mm2. Perfusion parameters were evaluated with “NordicICE” software. The map of D + D* was compared qualitatively with the perfusion map computed from the Gd scan. D + D* values of the cortex and medulla were in the range 2.3–2.7 and 1.1–1.6 × 10-3 mm2/s, respectively. In conclusion, in this pilot study a good qualitative relation between IVIM variables D + D* and renal perfusion has been found.
|
|
| 38. |
- Eckerbom, Per, 1974-, et al.
(författare)
-
Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
- 2019
-
Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:4, s. F693-F702
-
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.
|
|
| 39. |
- Eckerbom, Per, et al.
(författare)
-
Reduced Renal Apparent Diffusion Coefficient at Follow Up after COVID-19 Associated Acute Kidney Injury
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe Corona virus disease 2019 (COVID-19) with acute kidney injury (AKI) increases the risk of developing chronic kidney disease (CKD). In the present study we aimed to investigate the effects of severe COVID-19 on renal blood flow, perfusion, oxygenation and tissue characteristics in recovered patients using noninvasive multiparametric magnetic resonance imaging (MRI). Twenty-two patients, previously treated in the intensive care unit for COVID-19 were stratified depending on their degree of AKI during hospitalization. Patients without AKI were matched with those with AKI grade 1 and AKI grade 3 regarding age, sex, height, weight, body surface area (BSA) and body mass index (BMI). All patients had a normal measurement of creatinine within two years before hospitalization. An MRI scan was conducted 21±6 weeks after the first day of intensive care. Cortical and medullary apparent diffusion coefficients (ADC) were significantly lower in the ´AKI grade 3´group compared to the ´no AKI´ group, 1.83±0.11 vs 2.16±0.13 x 10-3 mm2/s (p=0.001) for cortex and 1.84±0.04 vs 2.09±0.13 x 10-3 mm2/s (p=0.007) for medulla. Also, total renal blood flow (tRBF) and global perfusion were significantly lower in the ´AKI grade 3´ group compared to the ´no AKI´ group. No differences regarding renal oxygenation, T1 or T2 were found. We conclude that patients treated for severe COVID-19 with high grade AKI, show decreased cortical and medullary ADC and reduced total renal blood flow and global perfusion compared to similar patients without AKI at follow up approximately five months after intensive care. These findings might indicate incipient development of renal fibrosis.
|
|
| 40. |
- Edlund, Jenny, et al.
(författare)
-
Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging
- 2009
-
Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 199-204
-
Tidskriftsartikel (refereegranskat)abstract
- By applying invasive techniques for direct measurements of oxygen tension, we have reported decreased kidney oxygenation in experimental diabetes in rats. However, the non-invasive MRI technique utilizing the BOLD effect provides several advantages with the possibility to perform repetitive measurements in the same animals and in human subjects. In this study, we applied a modified single gradient echo micro-imaging sequence to detect the BOLD effect in kidneys of diabetic rats and compared the results to normoglycemic controls. All measurements were performed on inactin-anaesthetized adult male Wistar Furth rats. Diabetes was induced by streptozotocin (45 mg/kg) 14 days prior to MRI-analysis. Sixteen T2*-weighted image records (B0=1.5 T) were performed using radiofrequency spoiled gradient echo sequence with 2.6 ms step increments of TE (TE1=12 ms), while TR (75 ms) and bandwidth per pixel (71.4 Hz) were kept constant. T2* maps were computed by mono-exponential fitting of the pixel intensities. Relaxation rates R2* (1/T2*) in cortex and outer stripe of the outer medulla were similar in both groups (cortex for controls 22.3 +/- 0.4 vs. diabetics 23.1 +/- 1.8 Hz and outer stripe of outer medulla for controls 24.9 +/- 0.4 vs. diabetics 26.4 +/- 1.8 Hz; n=4 in both groups), whereas R2* was increased in the inner stripe of the outer medulla in diabetic rats (diabetics 26.1 +/- 2.4 vs. controls 18.8 +/- 1.4 Hz; n=4, P<0.05). This study demonstrates that experimental diabetes in rats induces decreased oxygenation of the renal outer medulla. Furthermore, the proposed T2*-weighted MR micro-imaging technique is suitable for detection of regional changes in kidney oxygenation in experimental animal models.
|
|
| 41. |
- Edlund, Jenny, et al.
(författare)
-
The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney
- 2010
-
Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 26:5, s. 349-356
-
Tidskriftsartikel (refereegranskat)abstract
- Background Sustained hyperglycaemia induces increased renal oxygen consumption resulting in reduced oxygen availability in the diabetic kidney. We investigated the roles of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the neuronal nitric oxide synthase (nNOS) for the increased oxygen consumption in streptozotocin-diabetic rats.MethodsOxygen consumption was measured in isolated proximal tubular cells (PTC) from streptozotocin-induced diabetic rats (n = 7-9 per group) with and without chronic treatment with apocynin, a NADPH-oxidase inhibitor, or S-methyl-L-thiocitrulline (SMTC), a selective nNOS inhibitor, or a combination of the two and the results were compared to normoglycaemic controls (n = 10). Oxidative stress was estimated from thiobarbituric acid reactive substances and protein expression measured by Western blot.ResultsProximal tubular cells from untreated diabetic rats had increased oxygen consumption compared to controls (40.6 +/- 7.9 versus 10.9 +/- 2.0 nmol/mg protein/min). All treatments reduced the diabetes-induced increase in oxygen consumption (apocynin 10.5 +/- 1.7, SMTC 19.7 +/- 3.0 and apocynin +/- SMTC 21.6 +/- 3.6 nmol/mg protein/min). Neither apocynin nor SMTC had any effect on the oxygen consumption in cells pre-incubated with ouabain, an inhibitor of active electrolyte transport. Oxidative stress was elevated in the diabetic kidney and inhibited by all treatments. The increased oxygen consumption by diabetic proximal tubular cells correlated with increased protein expressions of p47phox and nNOS and the treatments prevented these increases.ConclusionsDiabetes induces oxidative stress, which increases oxygen consumption in proximal tubular cells. Inhibition of either NADPH-oxidase or nNOS prevented the increased oxygen consumption. The effect of blocking both these enzymes was less than additive suggesting overlapping pathways which warrant further studies.
|
|
| 42. |
- Edlund, Lars-Erik, 1953-, et al.
(författare)
-
Diabas – nordisk ordgeografisk databas
- 2012
-
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
|
|
| 43. |
- Edwards, Aurelie, et al.
(författare)
-
A model of mitochondrial O-2 consumption and ATP generation in rat proximal tubule cells
- 2020
-
Ingår i: American Journal of Physiology - Renal Physiology. - : AMER PHYSIOLOGICAL SOC. - 1931-857X .- 1522-1466. ; 318:1, s. F248-F259
-
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.
|
|
| 44. |
- Ek, Sverker R, 1930-, et al.
(författare)
-
Hjalmar Bergman : korrespondenser 1900-1930
- 2012
-
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
|
|
| 45. |
- Elksnis, Andris, et al.
(författare)
-
Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK
- 2021
-
Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 135:19, s. 2243-2263
-
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.
|
|
| 46. |
- Esbjörnsson, Joakim, et al.
(författare)
-
Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau : a prospective open cohort study
- 2019
-
Ingår i: The Lancet HIV. - : The Lancet Publishing Group. - 2405-4704 .- 2352-3018. ; 6:1, s. E25-E31
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.
|
|
| 47. |
|
|
| 48. |
- Franzen, Stephanie, et al.
(författare)
-
Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes
- 2014
-
Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 306:10, s. F1171-F1178
-
Tidskriftsartikel (refereegranskat)abstract
- One-third of diabetes mellitus patients develop diabetic nephropathy, and with underlying mechanisms unknown it is imperative that diabetic animal models resemble human disease. The present study investigated the susceptibility to develop diabetic nephropathy in four commonly used and commercially available mouse strains with type 1 diabetes to determine the suitability of each strain. Type 1 diabetes was induced in C57Bl/6, NMRI, BALB/c, and 129Sv mice by alloxan, and conscious glomerular filtration rate, proteinuria, and oxidative stress levels were measured in control and diabetic animals at baseline and after 5 and 10 wk. Histological alterations were analyzed using periodic acid-Schiff staining. Diabetic C57Bl/6 displayed increased glomerular filtration rate, i.e., hyperfiltration, whereas all other parameters remained unchanged. Diabetic NMRI developed the most pronounced hyperfiltration as well as increased oxidative stress and proteinuria but without glomerular damage. Diabetic BALB/c did not develop hyperfiltration but presented with pronounced proteinuria, increased oxidative stress, and glomerular damage. Diabetic 129Sv displayed proteinuria and increased oxidative stress without glomerular hyperfiltration or damage. However, all strains displayed intras-train correlation between oxidative stress and proteinuria. In conclusion, diabetic C57Bl/6 and NMRI both developed glomerular hyperfiltration but neither presented with histological damage, although NMRI developed low-degree proteinuria. Thus these strains may be suitable when investigating the mechanism causing hyperfiltration. Neither BALB/c nor 129Sv developed hyperfiltration although both developed pronounced proteinuria. However, only BALB/c developed detectable histological damage. Thus BALB/c may be suitable when studying the roles of proteinuria and histological alterations for the progression of diabetic nephropathy.
|
|
| 49. |
|
|
| 50. |
- Franzen, Stephanie, et al.
(författare)
-
Endothelin type A receptor inhibition normalises intrarenal hypoxia in rats used as a model of type 1 diabetes by improving oxygen delivery
- 2015
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 58:10, s. 2435-2442
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Intrarenal tissue hypoxia, secondary to increased oxygen consumption, has been suggested as a unifying mechanism for the development of diabetic nephropathy. Increased endothelin-1 signalling via the endothelin type A receptor (ETA-R) has been shown to contribute to the development of chronic kidney disease, but its role in kidney oxygen homeostasis is presently unknown. Methods The effects of acute ETA-R inhibition (8 nmol/l BQ-123 for 30-40 min directly into the left renal artery) on kidney function and oxygen metabolism were investigated in normoglycaemic control and insulinopenic male Sprague Dawley rats (55 mg/kg streptozotocin intravenously 2 weeks before the main experiment) used as a model of type 1 diabetes. Results Local inhibition of ETA-R in the left kidney did not affect BP in either the control or the diabetic rats. As previously reported, diabetic rats displayed increased kidney oxygen consumption resulting in tissue hypoxia in both the kidney cortex and medulla. The inhibition of ETA-Rs restored normal kidney tissue oxygen availability in the diabetic kidney by increasing renal blood flow, but did not affect oxygen consumption. Furthermore, ETA-R inhibition reduced the diabetes-induced glomerular hyperfiltration and increased the urinary sodium excretion. Kidney function in normoglycaemic control rats was largely unaffected by BQ-123 treatment, although it also increased renal blood flow and urinary sodium excretion in these animals. Conclusions/interpretation Acutely reduced intrarenal ETA-R signalling results in significantly improved oxygen availability in the diabetic kidney secondary to elevated renal perfusion. Thus, the beneficial effects of ETA-R inhibition on kidney function in diabetes may be due to improved intrarenal oxygen homeostasis.
|
|
