| 1. |
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| 2. |
- Ahlgren, Ulf, et al.
(author)
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Approaches for imaging islets
- 2010
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In: Advances in Experimental Medicine and Biology. - Dordrecht : Springer Netherlands. - 0065-2598 .- 2214-8019. ; 654, s. 39-57
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Journal article (peer-reviewed)abstract
- The establishment of improved technologies for imaging of the pancreas is a key element in addressing several aspects of diabetes pathogenesis. In this respect, the development of a protocol that allows for non-invasive scoring of human islets, or islet beta-cells, is of particular importance. The development of such a technology would have profound impact on both clinical and experimental medicine, ranging from early diagnosis of diabetes to the evaluation of therapeutic regimes. Another important task is the development of modalities for high-resolution imaging of experimental animal models for diabetes. Rodent models for diabetes research have for decades been instrumental to the diabetes research community. The ability to image, and to accurately quantify, key players of diabetogenic processes with molecular specificity will be of great importance for elucidating mechanistic aspects of the disease. This chapter aims to overview current progress within these research areas.
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| 3. |
- Alstermark, Bror, et al.
(author)
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Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey.
- 2002
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In: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 508, s. 281-97
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Journal article (peer-reviewed)abstract
- The literature on premotoneuronal and direct corticomotoneuronal (CM) control in the cat and macaque monkey is reviewed. The available experimental findings are not in accordance with a recently proposed hypothesis that direct CM connections have "replaced" the premotoneuronal pathways. Instead, we propose that premotoneuronal CM control plays an important role in motor control also in primates and that the direct CM connection has been added during phylogeny.
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| 4. |
- Bengtsson, Finn
(author)
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Brain tryptophan/serotonin perturbations in metabolic encephalopathy and the hazards involved in the use of psychoactive drugs
- 1999
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In: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 467, s. 139-154
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Journal article (peer-reviewed)abstract
- Several combined pathogenetic factors such as hyperammonemia, different brain tryptophan metabolic disturbancies and serotonin physiological/pharmacological alterations not yet defined in all details, will often give rise to the clinical neuropsychiatric condition known as hepatic encephalopathy (HE). Indeed, to this the probable exposure to novel potent CNS-monoamine acting drugs today may put such patients at certain risk for other pharmacodynamic (PD) responses than usually are expected from these "safe" drugs. Moreover, with a compromised liver function in HE, also pharmacokinetic (PK) features for the drugs are likely changed in these patients. Thus, the ultimate clinical outcome by this probable but unknown PD/PK-deviation for such psychoactive drugs when given to HE-patients needs further clarifrcation. Accordingly, delineation of both PD- and PK-effects in experimental HE should shed light on this issue of relevance for monoamine-active drug safety as well as on some further details in the complex tryptophan/monoamine-related pathophysiology that comes into play in HE.
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| 5. |
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| 6. |
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| 7. |
- Bölükbas, Deniz A., et al.
(author)
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Current and Future Engineering Strategies for ECMO Therapy
- 2023
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In: Advances in Experimental Medicine and Biology. - 2214-8019 .- 0065-2598. ; 1413, s. 313-326
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Book chapter (peer-reviewed)abstract
- Extracorporeal membrane oxygenation (ECMO) is a last resort therapy for patients with respiratory failure where the gas exchange capacity of the lung is compromised. Venous blood is pumped through an oxygenation unit outside of the body where oxygen diffusion into the blood takes place in parallel to carbon dioxide removal. ECMO is an expensive therapy which requires special expertise to perform. Since its inception, ECMO technologies have been evolving to improve its success and minimize the complications associated with it. These approaches aim for a more compatible circuit design capable of maximum gas exchange with minimal need for anticoagulants. This chapter summarizes the basic principles of ECMO therapy with the latest advancements and experimental strategies aiming for more efficient future designs.
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| 8. |
- Cerenius, Lage, et al.
(author)
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Crustacean Immunity
- 2010
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In: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 708, s. 239-259
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Journal article (peer-reviewed)abstract
- This chapter provides a review of recent progress in the elucidation of innate immune mechanisms in crustaceans. Mainly due to the importance of crustacean aquaculture interest in this field is large and the subject for extensive research efforts. Here, we provide detailed data on the molecular characterisation of lectins, antiviral reactions, hemocyte formation and differentiation and on the regulation of innate immune pathways.
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| 9. |
- Chinga-Carrasco, Gary, et al.
(author)
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Nanocelluloses – Nanotoxicology, Safety Aspects and 3D Bioprinting
- 2022
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In: Advances in Experimental Medicine and Biology. - Cham : Springer. - 0065-2598 .- 2214-8019. ; 1357, s. 155-177
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Journal article (peer-reviewed)abstract
- Nanocelluloses have good rheological properties that facilitate the extrusion of nanocellulose gels in micro-extrusion systems. It is considered a highly relevant characteristic that makes it possible to use nanocellulose as an ink component for 3D bioprinting purposes. The nanocelluloses assessed in this book chapter include wood nanocellulose (WNC), bacterial nanocellulose (BNC), and tunicate nanocellulose (TNC), which are often assumed to be non-toxic. Depending on various chemical and mechanical processes, both cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC) can be obtained from the three mentioned nanocelluloses (WNC, BNC, and TNC). Pre/post-treatment processes (chemical and mechanical) cause modifications regarding surface chemistry and nano-morphology. Hence, it is essential to understand whether physicochemical properties may affect the toxicological profile of nanocelluloses. In this book chapter, we provide an overview of nanotoxicology and safety aspects associated with nanocelluloses. Relevant regulatory requirements are considered. We also discuss hazard assessment strategies based on tiered approaches for safety testing, which can be applied in the early stages of the innovation process. Ensuring the safe development of nanocellulose-based 3D bioprinting products will enable full market use of these sustainable resources throughout their life cycle.
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| 10. |
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| 11. |
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| 12. |
- Daşu, Alexandru, et al.
(author)
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The relationship between vascular oxygen distribution and tissue oxygenation
- 2009
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In: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 255-260
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Journal article (peer-reviewed)abstract
- Tumour oxygenation could be investigated through several methods that use various measuring principles and can therefore highlight its different aspects. The results have to be subsequently correlated, but this might not be straightforward due to intrinsic limitations of the measurement methods. This study describes an analysis of the relationship between vascular and tissue oxygenations that may help the interpretation of results. Simulations have been performed with a mathematical model that calculates the tissue oxygenation for complex vascular arrangements by taking into consideration the oxygen diffusion into the tissue and its consumption at the cells. The results showed that while vascular and tissue oxygenations are deterministically related, the relationship between them is not unequivocal and this could lead to uncertainties when attempting to correlate them. However, theoretical simulation could bridge the gap between the results obtained with various methods.
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| 13. |
- Daşu, Alexandru, et al.
(author)
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Theoretical simulation of tumour oxygenation--practical applications
- 2006
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In: Advances in Experimental Medicine and Biology. - : Springer US. - 0065-2598 .- 2214-8019. ; 578, s. 357-362
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Journal article (peer-reviewed)abstract
- Theoretical simulation of tissue oxygenation is a robust method that can be used to quantify the tissue oxygenation for a variety of applications. However, it is necessary that the relevant input parameters are used for the model describing the tumour microenvironment. The results of the simulations presented in this article suggest that the accuracy of the simulations depends very much on the method of calculation of the effects of the temporal change of the hypoxic pattern due to the opening and the closure of blood vessels. Thus, the use of average oxygenations might lead to dangerous overestimations of the treatment response. This indicates that care should be taken when incorporating hypoxia information into the biological modelling of tumour response.
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| 14. |
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| 15. |
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| 16. |
- Eckerbom, Per, 1974-, et al.
(author)
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Intravoxel Incoherent Motion MR Imaging of the Kidney : Pilot Study
- 2013
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In: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598 .- 2214-8019. ; 765, s. 55-58
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Journal article (peer-reviewed)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.
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| 17. |
- Edlund, Jenny, et al.
(author)
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Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging
- 2009
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In: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 199-204
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Journal article (peer-reviewed)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.
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| 18. |
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| 19. |
- Franzen, Stephanie, et al.
(author)
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Repetitive Measurements of Intrarenal Oxygenation In Vivo Using L Band Electron Paramagnetic Resonance
- 2014
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In: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598 .- 2214-8019. - 9781493906208 - 9781493905836 ; 812, s. 135-141
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Journal article (peer-reviewed)abstract
- Intrarenal oxygenation is heterogeneous with oxygen levels normally being highest in the superficial cortex and lowest in the inner medulla. Reduced intrarenal oxygenation has been implied in the pathology of several kidney diseases. However, there is currently no method available to repetitively monitor regional renal oxygenation using minimally invasive procedures. We therefore evaluated implantable lithium phthalocyanine (LiPc) probes, which display a close correlation between EPR line width and oxygen availability. LiPc probes were implanted in the kidney cortex and medulla in the same mouse and sEPR spectra were acquired using a L band scanner during inhalation of air (21 % oxygen) or a mixture of air and nitrogen (10 % oxygen). In order to separate the signals from the two probes, a 1 G/cm gradient was applied and the signals were derived from 40 consecutive sweeps. Peak-to-peak comparison of the EPR line was used to convert the signal to an approximate oxygen tension in MATLAB. Kidney cortex as well as medullary oxygenation was stable over the 45 day period (cortex 56 +/- 7 mmHg and medulla 43 +/- 6 mmHg). However, 10 % oxygen inhalation significantly reduced oxygenation in both cortex (56 +/- 6 to 34 +/- 2 mmHg n = 15 p < 0.05) and medulla (42 +/- 5 to 29 +/- 3 mmHg n = 7 p < 0.05). In conclusion, L band EPR using LiPc probes implanted in discrete intrarenal structures can be used to repetitively monitor regional renal oxygenation. This minimally invasive method is especially well suited for conditions of reduced intrarenal oxygenation since this increases the signal intensity which facilitates the quantification of the EPR signal to absolute oxygenation values.
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| 20. |
- Friederich, Malou, 1983-, et al.
(author)
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Identification and distribution of uncoupling protein isoforms in the normal and diabetic rat kidney
- 2009
-
In: Advances in Experimental Medicine and Biology. - New York : Springer. - 0065-2598 .- 2214-8019. - 9780387859972 ; 645, s. 205-212
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Journal article (peer-reviewed)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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| 21. |
- Friederich, Malou, et al.
(author)
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Uncoupling protein-2 in diabetic kidneys : increased protein expression correlates to increased non-transport related oxygen consumption
- 2008
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In: Advances in Experimental Medicine and Biology. - Boston, MA : Springer Berlin/Heidelberg. - 0065-2598 .- 2214-8019. ; 614, s. 37-43, s. 37-43
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Journal article (peer-reviewed)abstract
- Diabetic patients have an elevated risk to develop renal dysfunction and it has been postulated that altered energy metabolism is involved. We have previously shown that diabetic rats have markedly decreased oxygen availability in the kidney, resulting from increased oxygen consumption. A substantial part of the increased oxygen consumption is unrelated to tubular transport, suggesting decreased mitochondrial efficiency. In this study, we investigated the protein expression of mitochondrial uncoupling protein (UCP)-2 in kidney tissue from control and streptozotocin (STZ)-induced diabetic rats. Protein levels of UCP-2 were measured in adult male control and STZ-diabetic Wistar Furth as well as Sprague Dawley rats in both the kidney cortex and medulla by Western blot technique. Two weeks of hyperglycemia resulted in increased protein levels of UCP-2 in kidneys from both Wistar Furth and Sprague Dawley rats. Both cortical and medullary UCP-2 levels were elevated 2-3 fold above control levels. We conclude that sustained STZ-induced hyperglycemia increases the kidney levels of mitochondrial UCP-2, which could explain the previously reported increase in non-transport related oxygen consumption in diabetic kidneys. The elevated UCP-2 levels may represent an effort to reduce the increased production of superoxide radicals which is evident during diabetes.
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| 22. |
- Friederich-Persson, Malou, et al.
(author)
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Angiotensin II Reduces Transport-Dependent Oxygen Consumption but Increases Transport-Independent Oxygen Consumption in Immortalized Mouse Proximal Tubular Cells
- 2014
-
In: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598 .- 2214-8019. - 9781493906208 - 9781493905836 ; 812, s. 157-163
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Journal article (peer-reviewed)abstract
- Oxidative stress is closely associated with renal dysfunction following diabetes and hypertension. Angiotensin II (Ang II) can activate the NADPH-oxidase, increasing oxidative stress that is thought to blunt proximal tubular electrolyte transport and thereby oxygen consumption (QO(2)). We investigated the effect of Ang II on QO(2) in immortalized mouse proximal tubular cells over-expressing the NADPH oxidase subunit p22(phox); a model of increased oxidative stress. Cultured cells were exposed to either Ang II or H2O2 for 48 h. QO(2) was determined during baseline (113 mmol/l NaCl; transport-dependent QO(2)) and during sodium-free conditions (transport-independent QO(2)). Ang II reduced transport-dependent QO(2) in wild-types, but not in p22(phox) which also displayed increased QO(2) at baseline. Transport-independent QO(2) was increased in p22(phox) and Ang II had no additional effect, whereas it increased QO(2) in wild-type. Addition of H2O2 reduced transport-dependent QO(2) in wild-types, but not in p22(phox). Transport-independent QO(2) was unaffected by H2O2. The similar effects of Ang II and H2O2 to reduce transport-dependent QO(2) suggest a direct regulatory role of oxidative stress. In accordance, the transport-dependent QO(2) was reduced in p22(phox) already during baseline. The effects of Ang II on transport-independent QO(2) was not replicated by H2O2, indicating direct regulation via Ang II-receptors independently of oxidative stress. However, the Ang II effect was absent in p22(phox), suggesting that oxidative stress also modulates normal Ang II signaling. In conclusion, Ang II affects both transport-dependent and transport-independent QO(2) in proximal tubular cells and may be an important pathway modulating renal QO(2).
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| 23. |
- Friederich-Persson, Malou, et al.
(author)
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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
-
In: 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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Journal article (peer-reviewed)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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| 24. |
- Gaceb, Abderahim, et al.
(author)
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Pericyte secretome
- 2018
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In: Pericyte Biology - Novel Concepts. - Cham : Springer International Publishing. - 0065-2598 .- 2214-8019. ; 1109, s. 139-163
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Book chapter (peer-reviewed)abstract
- The role of pericytes seems to extend beyond their known function in angiogenesis, fibrosis and wound healing, blood-brain barrier maintenance, and blood flow regulation. More and more data are currently accumulating indicating that pericytes, uniquely positioned at the interface between blood and parenchyma, secrete a large plethora of different molecules in response to microenvironmental changes. Their secretome is tissue-specific and stimulus-specific and includes pro- and anti-inflammatory factors, growth factors, and extracellular matrix as well as microvesicles suggesting the important role of pericytes in the regulation of immune response and immune evasion of tumors. However, the angiogenic and trophic secretome of pericytes indicates that their secretome plays a role in physiological homeostasis but possibly also in disease progression or could be exploited for regenerative processes in the future. This book chapter summarizes the current data on the secretory properties of pericytes from different tissues in response to certain pathological stimuli such as inflammatory stimuli, hypoxia, high glucose, and others and thereby aims to provide insights into the possible role of pericytes in these conditions.
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| 25. |
- Golovleva, Irina, et al.
(author)
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Mutation spectra in autosomal dominant and recessive retinitis pigmentosa in northern sweden.
- 2010
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In: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598 .- 2214-8019. ; 664, s. 255-262
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Journal article (peer-reviewed)abstract
- Retinal degenerations represent a heterogeneous group of disorders affecting the function of the retina. The frequency of retinitis pigmentosa (RP) is 1/3500 worldwide, however, in northern Sweden it is 1/2000 due to limited migration and a 'founder' effect. In this study we identified genetic mechanisms underlying autosomal dominant and recessive RP present in northern Sweden. Several novel mutations unique for this region were found. In an autosomal recessive form of RP, Bothnia dystrophy caused by mutations in the RLBP1 gene, bi-allelic mutations R234W, M226K and compound heterozygosity, M226K+R234W was detected.In dominant form of RP mapped to 19q13.42 a 59 kb genomic deletion including the PRPF31 and three other genes was found.These data provide additional information on the molecular mechanisms of RP evolvement and in the future might be useful in development of therapeutic strategies. Identification of the disease-causing mutations allowed introducing molecular genetic testing of the patients and their families into the clinical practice.
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