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  • 1.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Brain tryptophan/serotonin perturbations in metabolic encephalopathy and the hazards involved in the use of psychoactive drugs1999In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 467, p. 139-154Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Daşu, Alexandru
    et al.
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    The impact of tissue microenvironment on treatment simulation2003In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 510, p. 63-67Article in journal (Refereed)
  • 3.
    Daşu, Alexandru
    et al.
    Norrland University Hospital, Umeå.
    Toma-Daşu, Iuliana
    Stockholm University and Karolinska Institutet.
    The relationship between vascular oxygen distribution and tissue oxygenation2009In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 255-260Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Daşu, Alexandru
    et al.
    Umeå University.
    Toma-Daşu, Iuliana
    Umeå University.
    Theoretical simulation of tumour oxygenation--practical applications2006In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 578, no 12, p. 357-362Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Eckerbom, Per
    et al.
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Bjerner, Tomas
    Uppsala universitet, Enheten för radiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Weis, Jan
    Uppsala universitet, Enheten för radiologi.
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Intravoxel Incoherent Motion MR Imaging of the Kidney: Pilot Study2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 55-58Article in journal (Refereed)
    Abstract [en]

    MR examinations (Achieva 3 T, Philips, Best, The Netherlands) were performed at five different occasions in a healthy volunteer (male 60 years) and in one renal cancer patient (male 78 years) with normal renal function (creatinine 88 μmol/L). Intravoxel incoherent motion (IVIM) coefficients D + D* were measured using respiratory-triggered diffusion-weighted spin-echo echo-planar imaging. Perfusion data of the patient were acquired using a saturation-recovery gradient-echo sequence and with the bolus of Gd-BOPTA (Multihance). D + D* were computed by monoexponential fitting of MR signal intensity attenuation versus b for b = 0, 50, 100, 150 s/mm2. Perfusion parameters were evaluated with “NordicICE” software. The map of D + D* was compared qualitatively with the perfusion map computed from the Gd scan. D + D* values of the cortex and medulla were in the range 2.3–2.7 and 1.1–1.6 × 10-3 mm2/s, respectively. In conclusion, in this pilot study a good qualitative relation between IVIM variables D + D* and renal perfusion has been found.

  • 6.
    Edlund, Jenny
    et al.
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Fasching, Angelica
    Uppsala universitet, Integrativ Fysiologi.
    Liss, Per
    Uppsala universitet, Integrativ Fysiologi.
    Weis, Jan
    Uppsala universitet, Enheten för radiologi.
    Glickson, Jerry D.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging2009In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 199-204Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Franzén, Stephanie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Pihl, Liselotte
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Khan, Nadeem
    Geisel School Med, NH USA.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Uppsala, Sweden .
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering.
    Repetitive Measurements of Intrarenal Oxygenation In Vivo Using L Band Electron Paramagnetic Resonance2014In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 812, p. 135-141Article in journal (Refereed)
    Abstract [en]

    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 less than 0.05) and medulla (42 +/- 5 to 29 +/- 3 mmHg n = 7 p less than 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.

  • 8.
    Friederich, Malou
    et al.
    Uppsala universitet, Integrativ Fysiologi.
    Nordquist, Lina
    Uppsala universitet, Integrativ Fysiologi.
    Olerud, Johan
    Uppsala universitet, Neuroanatomi.
    Johansson, Magnus
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Identification and distribution of uncoupling protein isoforms in the normal and diabetic rat kidney2009In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 205-212Article in journal (Refereed)
    Abstract [en]

    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.

  • 9. Friederich, Malou
    et al.
    Olerud, Johan
    Fasching, Angelica
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Palm, Fredrik
    Uncoupling protein-2 in diabetic kidneys: increased protein expression correlates to increased non-transport related oxygen consumption2008In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 614, p. 37-43Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Friederich-Persson, Malou
    et al.
    Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Sweden.
    Persson, Patrik
    Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Sweden.
    Fasching, Angelica
    Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Sweden.
    Hansell, Peter
    Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Sweden.
    Nordquist, Lina
    Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Sweden.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Medical Cell Biology, Div. Integrative Physiology, Uppsala University, Biomedical Center.
    Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage: effects of triiodothyronine and dinitrophenol in normoglycemic rats.2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 789, p. 9-14Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Friederich-Persson, Malou
    et al.
    Uppsala University, Sweden.
    Welch, William J.
    Georgetown University, DC 20007 USA.
    Luo, Zaiming
    Georgetown University, DC 20007 USA.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Nordquist, Lina
    Uppsala University, Sweden.
    Angiotensin II Reduces Transport-Dependent Oxygen Consumption but Increases Transport-Independent Oxygen Consumption in Immortalized Mouse Proximal Tubular Cells2014In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 812, p. 157-163Article in journal (Refereed)
    Abstract [en]

    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).

  • 12.
    Hammarström, Sven
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Trinks, Cecilia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Wigren, Jane
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Surapureddi, S
    Söderström, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Glass, CK
    Novel eicosanoid activators of PPAR? formed by raw 264.7 macrophage cultures2002In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 507, p. 343-349Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 13.
    Hammarström, Sven
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Trinks, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wigren, Jane
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Surapureddi, Sailesh
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Glass, Christopher K
    University of California, San Diego, Jolla, CA, USA.
    Novel eicosanoid activators of PPAR gamma formed by RAW 264.7 macrophage cultures2002In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 507, p. 343-349Article in journal (Refereed)
  • 14.
    Herbertsson, Helena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kühme, Tobias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Hammarström, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    A 12(S)-HETE receptor in Lewis lung carcinoma cells.1999In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 447, p. 193-198Article in journal (Other academic)
  • 15.
    Herbertsson, Helena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kühme, Tobias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Hammarström, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Subunits and cellular occurrence of the 12(S)-HETE binding complex2000In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 469, p. 253-258Article in journal (Other academic)
  • 16.
    Liss, Per
    et al.
    Uppsala universitet, Enheten för radiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Fasching, Angelica
    Uppsala universitet, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Iodinated contrast media decrease renomedullary blood flow. A possible cause of contrast media-induced nephropathy2009In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 213-218Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Lolas, Georgios
    et al.
    Athens School Med, Greece.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
    Bourantas, George C.
    University of Luxembourg, Luxembourg.
    Tsikourkitoudi, Vasiliki
    Athens School Med, Greece.
    Syrigos, Konstantinos
    Athens School Med, Greece.
    Modeling Proteolytically Driven Tumor Lymphangiogenesis2016In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 936, p. 107-136Article in journal (Refereed)
    Abstract [en]

    With the exception of a limited number of sites in the body, primary tumors infrequently lead to the demise of cancer patients. Instead, mortality and a significant degree of morbidity result from the growth of secondary tumors in distant organs. Tumor survival, growth and dissemination are associated with the formation of both new blood vessels (angiogenesis) and new lymph vessels (lymphagenesis or lymphangiogenesis). Although intensive research in tumor angiogenesis has been going on for the past four decades, experimental results in tumor lymphangiogenesis began to appear only in the last 10 years. In this chapter we expand the models proposed by Friedman, Lolas and Pepper on tumor lymphangiogenesis mediated by proteolytically and un-proteolytically processed growth factors (Friedman and Lolas G, Math Models Methods Appl Sci 15(01): 95-107, 2005; Pepper and Lolas G, Selected topics in cancer modeling: genesis, evolution, immune competition, and therapy. In: The lymphatic vascular system in lymphangiogenesis invasion and metastasis a mathematical approach. Birkhauser Boston, Boston, pp 1-22, 2008). The variables represent different cell densities and growth factors concentrations, and where possible the parameters are estimated from experimental and clinical data. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous ("anarchic") spatio-temporal solutions. More specifically, we observed coherent masses of tumor clusters migrating around and within the lymphatic network. Our findings are in line with recent experimental evidence that associate cluster formation with the minimization of cell loss favoring high local extracellular matrix proteolysis and thus protecting cancer invading cells from an immunological assault driven by the lymphatic network.

  • 18. Martensson, LGE
    et al.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    A pharmacological interaction between melatonin and the alpha(2)-adrenoceptor in cuckoo wrasse melanophores1999In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 460, p. 221-228Article in journal (Refereed)
  • 19. Nilsson Ekdahl, Kristina
    et al.
    Henningsson, Anna J
    IKE Jönköping.
    Sandholm, Kerstin
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Immunity in Borreliosis with special emphasis on the role of complement.2007In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 598, p. 198-213Article, review/survey (Refereed)
  • 20.
    Nordquist, Lina
    et al.
    Division of Integrative Physiology, Departments of Medical Cell Biology, Uppsala University.
    Liss, Per
    Radiology, Oncology and Radiation Science, Uppsala University.
    Fasching, Angelica
    Division of Integrative Physiology, Departments of Medical Cell Biology, Uppsala University.
    Hansell, Peter
    Division of Integrative Physiology, Departments of Medical Cell Biology, Uppsala University.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Division of Integrative Physiology, Departments of Medical Cell Biology, Uppsala University, Biomedical Center.
    Hypoxia in the diabetic kidney is independent of advanced glycation end-products.2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 185-193Article in journal (Refereed)
    Abstract [en]

    Sustained hyperglycemia is closely associated with increased risk to develop nephropathy. We have previously reported alterations in the intrarenal oxygen metabolism already after the early onset of diabetes. Furthermore, formation of advanced glycation end-products (AGE) is postulated as a major contributor to diabetic nephropathy. We therefore investigated the possible relationship between altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and streptozotocin-diabetic rats with and without chronic treatment with aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N(6)-(1-Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was estimated by inulin clearance, oxygen tension (pO(2)) and interstitial pH by microelectrodes and regional renal blood flow (RBF) by laser-Doppler. Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration was unaffected by aminoguanidine, whereas L-NIL normalized GFR in diabetic rats. pO(2) and interstitial pH, but not RBF, were lower in both kidney cortex and medulla compared to control rats, but was unaffected by both chronic treatments. Urinary protein excretion was higher in diabetic rats and unaffected by L-NIL, whereas aminoguanidine paradoxically increased this parameter. Damage scores were similar in all groups.In conclusion, diabetes-induced alterations in intrarenal oxygen metabolism are independent of the AGE pathway, and precede any morphological changes. These findings highlight the early stage of diabetes as being a metabolic disorder also in the kidney.

  • 21.
    Palm, Fredrik
    et al.
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Fasching, Angelica
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Hansell, Peter
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Liss, Per
    Uppsala universitet, Enheten för radiologi.
    Diabetes-induced decrease in renal oxygen tension: effects of an altered metabolism2006In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 578, p. 161-166Article in journal (Refereed)
    Abstract [en]

    During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

  • 22.
    Palm, Fredrik
    et al.
    Uppsala universitet, Integrativ Fysiologi.
    Nordquist, Lina
    Uppsala universitet, Integrativ Fysiologi.
    Buerk, Donald G.
    Nitric oxide in the kidney: Direct measurements of bioavailable renal nitric oxide2008In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 599, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Increasing efforts have been directed towards investigating the involvement of nitric oxide (NO) for normal kidney function. Recently, a crucial role of NO in the development of progressive renal dysfunction has been reported during diabetes and hypertension. Indirect estimation of renal NO production include urinary nitrite/nitrate measurements, but there are several disadvantages of indirect methods since production and bioavailability of NO rarely coincide. Thus, direct measurement of in vivo NO bioavailability is preferred, although these methods are more time consuming and require highly specialized equipment and knowledge. This review focuses on two techniques for in vivo measurement of bioavailable NO in the kidney. We have applied Whalen-type recessed NO microsensors for measurement of NO in the kidney cortex, whereas the hemoglobin-trapping technique seems to be more suitable for NO measurement in the renal medulla. Both methods are robust and reliable, and we discuss advantages and shortcomings of each method.

  • 23.
    Persson, Malou Friederich
    et al.
    Division of Integrative Physiology, Department of Medical Cell Biology, Biomedical Center, Uppsala University.
    Welch, William J
    Division of Nephrology and Hypertension, Department of Medicine, Medical Center, Georgetown University.
    Wilcox, Christopher S
    Division of Nephrology and Hypertension, Department of Medicine, Medical Center, Georgetown University.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Divion of Integrative Physiology, Department of Medical Cell Biology, Biomedical Center, Uppsala University. Division of Nephrology and Hypertension, Department of Medicine, Medical Center, Georgetown University.
    Kidney function after in vivo gene silencing of uncoupling protein-2 in streptozotocin-induced diabetic rats.2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Kidney uncoupling protein 2 (UCP-2) increases in streptozotocin-induced diabetes, resulting in mitochondria uncoupling, i.e., increased oxygen consumption unrelated to active transport. The present study aimed to investigate the role of UCP-2 for normal and diabetic kidney function utilizing small interference RNA (siRNA) to reduce protein expression. Diabetic animals had increased glomerular filtration rate and kidney oxygen consumption, resulting in decreased oxygen tension and transported sodium per consumed oxygen. UCP-2 protein levels decreased 2 and 50% after UCP-2 siRNA administration in control and diabetic animals respectively. Kidney function was unaffected by in vivo siRNA-mediated gene silencing of UCP-2. The reason for the lack of effect of reducing UCP-2 is presently unknown but may involve compensatory mitochondrial uncoupling by the adenosine nucleotide transporter.

  • 24.
    Persson, Patrik
    et al.
    Department of Medical Cell Biology, Uppsala University.
    Hansell, Peter
    Department of Medical Cell Biology, Uppsala University.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Medical Cell Biology, Uppsala University.
    Adenosine A2 receptor-mediated regulation of renal hemodynamics and glomerular filtration rate is abolished in diabetes.2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 225-230Article in journal (Refereed)
    Abstract [en]

    Alterations in glomerular filtration rate (GFR) are one of the earliest indications of altered kidney function in diabetes. Adenosine regulates GFR through tubuloglomerular feedback mechanism acting on adenosine A1 receptor. In addition, adenosine can directly regulate vascular tone by acting on A1 and A2 receptors expressed in afferent and efferent arterioles. Opposite to A1 receptors, A2 receptors mediate vasorelaxation. This study investigates the involvement of adenosine A2 receptors in regulation of renal blood flow (RBF) and GFR in control and diabetic kidneys. GFR was measured by inulin clearance and RBF by a transonic flow probe placed around the renal artery. Measurements were performed in isoflurane-anesthetized normoglycemic and alloxan-diabetic C57BL/6 mice during baseline and after acute administration of 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2 receptor antagonist. GFR and RBF were lower in diabetic mice compared to control (258 ± 61 vs. 443 ± 33 μl min(-1) and 1,083 ± 51 vs. 1,405 ± 78 μl min(-1)). In control animals, DMPX decreased RBF by -6%, whereas GFR increased +44%. DMPX had no effects on GFR and RBF in diabetic mice. Sodium excretion increased in diabetic mice after A2 receptor blockade (+78%). In conclusion, adenosine acting on A2 receptors mediates an efferent arteriolar dilatation which reduces filtration fraction (FF) and maintains GFR within normal range in normoglycemic mice. However, this regulation is absent in diabetic mice, which may contribute to reduced oxygen availability in the diabetic kidney.

  • 25.
    Renz, Andrea
    et al.
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Burek, Christof Burek
    Institute of Experimental Dermatology, University of Muenster, Germany.
    Mier, Walter
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Mozoluk, Malgorzata
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Schulze-Osthoff, Klaus
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Los, Marek Jan
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Cytochrome c is rapidly extruded from apoptotic cells and detectable in serum of anticancer-drug treated tumor patients2001In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 495, p. 331-334Article in journal (Refereed)
  • 26.
    Segelmark, Mårten
    Lunds Universitet.
    ANCA and IgG subclasses. In: Gross WL, ed. ANCA Associated Vasculitides1993In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, no 336, p. 71-75Article in journal (Refereed)
  • 27.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Expression of Macrophage Antigens by Tumor Cells2011In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 714, p. 141-150Article in journal (Refereed)
    Abstract [en]

    Macrophages are a heterogeneous cell population of the myeloid linage derived from monocytes. These cells show two different polarization states, M1 and M2 macrophages in response to different micro environmental signals. Tumor associated macrophages (TAM) represent the M2 type and promote tumor progression. These cells express antigens that more or less are specific for macrophages like: CD14, CD68, MAC387, CD 163, and DAP12. In a series of recent studies it is shown that cancer cells may express these antigens and CD I 63, MAC387 and DAP12 may be expressed by e.g. breast cancer cells. Thus, 48% of the breast cancers expressed CD163 that is a scavenger receptor normally expressed by macrophages alone. The corresponding figure for rectal cancer is 31%. The expression of CD163 is correlated to early distant recurrence in breast cancer and local recurrence in rectal cancer and reduced survival time in both conditions. Expression of macrophage antigens in breast- and colorectal-cancers may have a prognostic relevance in clinical praxis. One explanation to these findings is that resemblance with macrophages may indicate a more invasive phenotype due to genetic exchange between the primary tumor cells and associated macrophages. This is further supported by the finding that expression of DAP12, a macrophage fusion receptor, in breast cancer is associated with an advanced tumor grade and higher rates of skeletal and liver metastases and overall shorter distant recurrence free survival. Another explanation to the changed phenotype is a genetic exchange between the cells by exosome-mediated transfer.

  • 28.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Caveolins and caveolae, roles in insulin signalling and diabetes2012In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 729, p. 111-126Article in journal (Refereed)
    Abstract [en]

    Much data in the scientific literature demonstrate a fundamental involvement of caveolae in insulin action, although particular aspects remain matters of debate. The insulin receptor and part of the downstream signalling mediators are localized in or recruited to caveolae. Moreover, as part of the signalling, insulin receptors are rapidly endocytosed by caveolae in response to the hormone. The insulin regulated glucose transporter GLUT4 appears to localize to caveolae after insulin-stimulated translocation to the plasma membrane, while the endocytosis of GLUT4 may involve a clathrin-mediated process. Insulin resistance due to dysfunction of insulin signalling in target tissues is a primary cornerstone of Type 2 diabetes. Lack of caveolae makes animals and human beings insulin resistant, but there is presently no evidence that caveolae play a role in the pathogenesis of insulin resistance in obesity and Type 2 diabetes.

  • 29.
    Tarkowski, Andrej
    et al.
    University of Gothenburg, Sweden.
    Verdrengh, Margareta
    University of Gothenburg, Sweden.
    Jonsson, Ing-Marie
    University of Gothenburg, Sweden.
    Magnusson, Mattias
    University of Gothenburg, Sweden.
    Foster, Simon J.
    University of Sheffield, UK .
    Liu, Zai-Quing
    University of Gothenburg, Sweden.
    Carbohydrates and biology of staphylococcal infections2005In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 564, p. 115-116Article in journal (Refereed)
  • 30.
    Toma-Dasu, Iuliana
    et al.
    Stockholm University and Karolinska Institutet, Stockholm, Sweden.
    Dasu, Alexandru
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Quantitative hypoxia imaging for treatment planning of radiotherapy2014In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 812, p. 143-148Article in journal (Refereed)
    Abstract [en]

    Tumour oxygenation is an important determinant of radiotherapy outcome as it could modulate cellular radiation sensitivity. Advanced PET imaging able to characterise this microenvironmental aspect in vivo might be used to devise counteracting therapies as it could provide information on the severity and the spatial distribution of the hypoxic regions. This study reviews the advantages and limitations of PET for imaging and quantifying tumour hypoxia and proposes a novel approach to obtain absolute levels of hypoxia from PET images through the use of EPR oximetry. This would offer a significant advantage over proposals based on empirical conversions of the intensities in the PET images to relative radiosensitivities. Thus, tumour hypoxia must be taken into account at the stage of treatment planning for photons and particle therapy by accounting for its extent and severity through the use of PET imaging combined with absolute EPR measurements.

  • 31.
    Toma-Daşu, Iuliana
    et al.
    Stockholm University and Karolinska Institutet.
    Daşu, Alexandru
    Norrland University Hospital.
    Brahme, Anders
    Karolinska Institutet.
    Quantifying tumour hypoxia by PET imaging--a theoretical analysis2009In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 645, p. 267-272Article in journal (Refereed)
    Abstract [en]

    Information on tumour oxygenation could be obtained from various imaging methods, but the success of incorporating it into treatment planning depends on the accuracy of quantifying it. This study presents a theoretical analysis of the efficiency of measuring tumour hypoxia by PET imaging. Tissue oxygenations were calculated for ranges of biologically relevant physiological parameters and were then used to simulate PET images for markers with different uptake characteristics. The resulting images were used to calculate dose distributions that could lead to predefined tumour control levels. The results have shown that quantification of tumour hypoxia with PET may lead to different values according to the tracer used and the tumour site investigated. This would in turn be reflected into the dose distributions recommended by the optimisation algorithms. However, irrespective of marker-specific differences, focusing the radiation dose to the hypoxic areas appears to reduce the average tumour dose needed to achieve a certain control level.

  • 32.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Karlsson, Mikael
    Umeå University.
    Theoretical simulation of tumour hypoxia measurements2006In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 578, no 12, p. 369-374Article in journal (Refereed)
    Abstract [en]

    Our simulations suggested that measurements performed in a limited number of points in the tumour can be representative for the situation in the whole tumour. It has further been shown that the polarographic electrode cannot be used to measure small regions of hypoxia. In fact it has been suggested that the most important factor that determines the efficiency of the polarographic electrode is the spatial distribution of the hypoxic cells and not their type, and therefore the polarographic electrode cannot be used to make the distinction between acute and chronic hypoxia. The simulations have also shown that it is reasonable to assume that the electrode measurement can be correlated to the situation in the whole tissue, even though the correlation is only qualitative. And because the electrode measurements are greatly influenced by the averaging process, the quantitative use of the electrode measurements may lead to erroneous results, especially for modelling the treatment response.

  • 33.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Waites, Anthony
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Computer simulation of oxygen microelectrode measurements in tissues2003In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 510, p. 157-161Article in journal (Refereed)
  • 34.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Is type 1 diabetes a disease of the gut immune system triggered by cow's milk insulin2005In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 569, p. 151-156Article in journal (Refereed)
  • 35.
    Wilcox, Christopher S
    et al.
    Kidney and Vascular Research Center, Georgetown University Hypertension.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Kidney and Vascular Research Center, Georgetown University Hypertension. Department of Medical Cell Biology, Uppsala University.
    Welch, William J
    Kidney and Vascular Research Center, Georgetown University Hypertension.
    Renal oxygenation and function of the rat kidney: effects of inspired oxygen and preglomerular oxygen shunting.2013In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 765, p. 329-334Article in journal (Refereed)
    Abstract [en]

    We investigated the hypothesis that a preglomerular diffusional shunt for O(2) stabilized renal PO(2) and that changes in intrarenal PO(2) determined nephron nitric oxide (NO) availability for blunting of the tubuloglomerular feedback (TGF) response. The inspired O(2) content of anesthetized rats was changed from normal (21%) to low (10%) or high (100%) for 30-45 min. Direct recordings of PO(2) in the lumens of proximal and distal tubules demonstrated significantly (P < 0.05) lower values at all sites in spontaneously hypertensive rats compared to normotensive Wistar Kyoto (WKY) rats. Low inspired O(2) did not change intratubular PO(2), but high inspired O(2) increased PO(2) modestly (25-50%; P < 0.01) in both strains and at both sites. Addition of 7-nitroindazole (7-NI; 10(-4) M) to artificial tubular fluid perfusing the loop of Henle of WKY nephrons to block neuronal (type 1) nitric oxide synthase in the macula densa increased TGF but this increase was less (P < 0.01) in nephrons of rats breathing high vs. normal inspired O(2) (1.8 ± 0.4 vs. 3.4 ± 0.3 mmHg; P < 0.01). In conclusion, the PO(2) in the renal tubules was effectively buffered from even extreme changes in arterial PO(2), consistent with a functionally important preglomerular O(2) diffusional shunt. However, high inspired PO(2) increased intratubular PO(2) sufficiently to blunt the effects of NO derived from the macula densa, likely reflecting bioinactivation of NO by reactive oxygen species generated at increased PO(2) levels. Thus, the preglomerular diffusional shunt appeared to stabilize intrarenal PO(2) during changes in arterial oxygen and to protect NO signaling within the kidney.

1 - 35 of 35
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