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  • 251.
    Weigl, Wojciech
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Adamski, Jan
    Satakunta Cent Hosp, Dept Anaesthesia & Intens Care, Pori, Finland.
    Goryński, Paweł
    Natl Inst Hyg, Natl Inst Publ Hlth, Ctr Monitoring & Anal Populat Hlth Status, Warsaw, Poland.
    Kański, Andrzej
    Med Univ Warsaw, Cent Teaching Hosp, Dept Anaesthesiol & Intens Care 2, Warsaw, Poland.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    ICU mortality and variables associated with ICU survival in Poland: A nationwide database study2018In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 35, no 12, p. 949-954Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recently published international comparison data across European countries revealed high mortality rates in Polish ICUs.

    OBJECTIVES: Estimation of the rate of ICU mortality and identification of variables associated with ICU survival in Poland.

    DESIGN: Retrospective analyses of a database reporting ICU stays in Poland.

    SETTINGS AND PATIENTS: The study included data from all adult patients admitted to an ICU in Poland from 1 January 2012 to 31 December 2012.

    MAIN OUTCOME MEASURES: ICU mortality and variables associated with ICU survival.

    RESULTS: A total of 48 282 patients were treated in 347 ICUs (mean age 63.1 ± 16.8 years, 59% men) with 20 278 deaths (42.0%). Variables associated with ICU survival were: tertiary level of hospital care [relative risk (RR) 0.86, 95% confidence interval (CI) 0.80 to 0.92, P < 0.001]; high annual patient volume in the ICU (RR 0.9995 patient year, 95% CI 0.9994 to 0.9996, P < 0.001); younger patient age (RR 1.025 year, 95% CI 1.024 to 1.026, P < 0.001); female sex (RR 0.92, 95% CI 0.88 to 0.96; P < 0.001); and lower number of comorbidities (RR 1.33, 95% CI 1.31 to 1.35, P < 0.001).

    CONCLUSION: ICU mortality was high in Poland. Structural variables, such as the level of hospital care and annual patient volume, may be associated with ICU survival.

  • 252.
    Weigl, Wojciech
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Adamski, Jan
    Goryński, Paweł
    Kański, Andrzej
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mortality rate is higher in Polish intensive care units than in other European countries.2017In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 43, no 9, p. 1430-1432Article in journal (Other academic)
  • 253. Wilcox, C. S.
    et al.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Welch, W. J.
    Renal oxygenation and function of the rat kidney: Effects of inspired oxygen and preglomerular oxygen shunting2013In: 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 &lt; 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 &lt; 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 &lt; 0.01) in nephrons of rats breathing high vs. normal inspired O 2 (1.8 ± 0.4 vs. 3.4 ± 0.3 mmHg; P &lt; 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.

  • 254.
    Wolgast, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Persson, Anders E. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    The gel hypothesis applied to the rat renal capillary membranes - a review2011In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no 4, p. 617-628Article, review/survey (Refereed)
    Abstract [en]

    In the gel model for the glomerular (and peritubular) capillary membrane, the integrity of the membrane is supposed to result from the fluid reabsorption induced by the osmotic action of the counter-ions attracted to negative fixed charges, increasing the gel pressure such that it becomes the same as in the capillaries. From this point on, the gel will be unaffected by the high capillary pressure. The same fluid reabsorption will also suspend the fibrils in the matrix such that they form a series of grids composed of, for example, horizontal fibrils spaced similarly from one another. The model thereby explains the well-known phenomenon of a uniform 'pore' size, although slits rather than pores constitute the transport routes. The model also explains the fact that the plasma proteins are free to move in the membrane matrix, which is the consequence of a recent finding that a major restriction to albumin is offered by a unique protein, nephrin, located between the podocytes in Bowman's space cells. A large molecule, which may become trapped in a slit between two fibrils, will thus push out the positive counter-ions whereby the charges become free and hence repel one another, widening the slit such that the molecule is free to move in any direction. It is furthermore concluded that the restriction to proteins is also dependent on the width of the slits closest to plasma.

  • 255. Yang, Ting
    et al.
    Huang, Liyue
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gao, Xiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Lundberg, Jon
    Weitzberg, Eddie
    Persson, Erik A. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    Role of gut microbiota in modulating the anti-inflammatory and antioxidative effects of dietary nitrate2013In: Nitric oxide, ISSN 1089-8603, E-ISSN 1089-8611, Vol. 31, no S1, p. S16-S16Article in journal (Other academic)
  • 256.
    Zang, Guangxiang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christoffersson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Tian, Geng
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Harun-Or-Rashid, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Vågesjö, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Barg, Sebastian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Aberrant association between vascular endothelial growth factor receptor-2 and VE-cadherin in response to vascular endothelial growth factor-a in Shb-deficient lung endothelial cells2013In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 25, no 1, p. 85-92Article in journal (Refereed)
    Abstract [en]

    Vascular permeability is a hallmark response to the main angiogenic factor VEGF-A and we have previously described a reduction of this response in Shb knockout mice. To characterize the molecular mechanisms responsible for this effect, endothelial cells were isolated from lungs and analyzed in vitro. Shb deficient endothelial cells exhibited less migration in a scratch wound-healing assay both under basal conditions and after vascular endothelial growth factor-A (VEGF-A) stimulation, suggesting a functional impairment of these cells in vitro. Staining for VE-cadherin and vascular endothelial growth factor receptor-2 (VEGFR-2) showed co-localization in adherens junctions and in intracellular sites such as the perinuclear region in wild-type and Shb knockout cells. VEGF-A decreased the VE-cadherin/VEGFR-2 co-localization in membrane structures resembling adherens junctions in wild-type cells whereas no such response was noted in the Shb knockout cells. VE-cadherin/VEGFR-2 co-localization was also recorded using spinning-disc confocal microscopy and VEGF-A caused a reduced association in the wild-type cells whereas the opposite pattern was observed in the Shb knockout cells. The latter expressed slightly more of cell surface VEGFR-2. VEGF-A stimulated extracellular-signal regulated kinase, Akt and Rac1 activities in the wild-type cells whereas no such responses were noted in the knockout cells. We conclude that aberrant signaling characteristics with respect to ERK, Akt and Rac1 are likely explanations for the observed altered pattern of VE-cadherin/VEGFR-2 association. The latter is important for understanding the reduced in vivo vascular permeability response in Shb knockout mice, a phenomenon that has patho-physiological relevance.

  • 257.
    Zhou, Suhan
    et al.
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Jiang, Shan
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Guo, Jie
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Xu, Nan
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Wang, Qin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Zhang, Gensheng
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Zhao, Liang
    Guangzhou Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou, Guangdong, Peoples R China; Charite Univ Med Berlin, Inst Vegetat Physiol, Berlin, Germany.
    Zhou, Qin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Fu, Xiaodong
    Guangzhou Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou, Guangdong, Peoples R China.
    Li, Lingei
    Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA;Georgetown Univ, Hypertens Res Ctr, Washington, DC USA.
    Patzak, Andreas
    Charite Univ Med Berlin, Inst Vegetat Physiol, Berlin, Germany.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lai, En Yin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1, Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China; Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA;Georgetown Univ, Hypertens Res Ctr, Washington, DC USA.
    ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 1, p. F134-F145Article in journal (Refereed)
    Abstract [en]

    Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Set(473) and eNOS at Ser(1177). Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis. and improving microvascular endothelial dysfunction. rhADAMIS13 could be a promising strategy to treat AKI in clinical settings.

  • 258.
    Öhnstedt, E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Vågesjö, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Lofton Tomenius, Hava
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Roos, S.
    Swedish Univ Agr Sci, Uppsala, Sweden.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Bioengineering of the local wound environment accelerates wound healing by increasing macrophage density and induces a phenotype shift in the wound macrophages2018In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no S1, p. 79-79Article in journal (Other academic)
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