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- Fenhammar, Johan
(författare)
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Renal failure in experimental sepsis : role of endothelin and the toll-like receptor 4
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis is the leading cause of renal failure in critically ill patients, but the pathogenesis of septic kidney dysfunction is poorly defined. The current paradigm states that hypoperfusion and excessive renal vasoconstriction results in renal ischemia. However, experimental data also exist indicating a direct immune-mediated basis of septic renal impairment. This thesis aimed to investigate the contribution of both a potent vasoconstrictor peptide, endothelin-1 (ET-1), and a receptor that activates the immune system in response to a bacterial infection, the Toll-like receptor 4 (TLR4), to the renal failure caused by sepsis. The first part of this thesis investigated the role of the endothelin system in renal microcirculatory and functional impairment caused by experimental septic renal failure, by studying the effects of dual endothelin type A and B (ETA/ETB) antagonism and selective ETA-antagonism during porcine endotoxemia. ET-1 is a vasoconstrictor peptide that is a potent modulator of microcirculatory blood flow. It is released in high amounts during sepsis and experimental data have shown that ET-1 reduces renal blood flow. In paper I and II pigs were subjected to lipopolysaccharide (LPS) infusion and the renal microcirculatory effects of dual ETA/ETB or selective ETA antagonism were investigated. The main findings were that dual ETA/ETB blockade attenuated the endotoxemia induced reduction in renal cortical microcirculation, as well as the increase in plasma creatinine levels (paper I). In addition, selective ETA antagonism reduced the decline in renal medullary microcirculation, but had no significant effect on diuresis or creatinine clearance (paper II). The second part of this thesis investigated the role of TLR4 activation in renal failure caused by hyperdynamic endotoxemia or sepsis. Conscious surgically prepared sheep were subjected to LPS or live Escherichia coli infusion and observed for 24-36 hours. A main finding was that pretreatment with a TLR4-inhibitor attenuated renal failure and hypotension caused by endotoxemia in sheep. This effect was greater compared to norepinephrine treatment, in a dose that prevented hypotension (paper III). Moreover, it was observed that septic renal failure developed without renal hypoperfusion and that treatment with a TLR4-inhibitor reversed renal failure when administered 12 hours into sepsis (paper IV). This effect was independent of changes in systemic or renal hemodynamics but was associated with a reduced renal neutrophil accumulation. In conclusion, despite no reduction in renal perfusion or arterial blood pressure, septic renal failure may still develop. During hyperdynamic sepsis, stimulation of the innate immune system, via TLR4 activation, may contribute to the development of renal failure. In addition, TLR4-inhibition is an effective treatment to improve renal function in ovine sepsis induced by E.coli. In hypodynamic endotoxemia, ET-1 contributes to renal vasoconstriction. By acting on ETA, ET-1 reduces renal medullary blood flow causing ischemia but has no short-term effect on renal function.
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- Lithner, Johan, 1960-
(författare)
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The Role of Exercises in Calculus Textbooks
- 2003
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper studies the discrepancy between the rich goals and the limited outcome in terms of reasoning required to do exercises.
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- Ruchon, Thierry, et al.
(författare)
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Macroscopic effects in attosecond pulse generation
- 2008
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- We examine how the generation and propagation of high-order harmonics in a partly ionized gas medium affect their strength and synchronization. The temporal properties of the resulting attosecond pulses generated in long gas targets can be significantly influenced by macroscopic effects, in particular by the intensity in the medium and the degree of ionization which control the dispersion. Under some conditions, the use of gas targets longer than the absorption length can lead to the generation of compressed attosecond pulses. We show these macroscopic effects experimentally, using a 6 mm-long argon-filled gas cell as the generating medium.
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- Allen, S. L., et al.
(författare)
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C-13 transport studies in L-mode divertor plasmas on DIII-D
- 2005
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 337-39:03-jan, s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- (CH4)-C-13 was injected with a toroidally-symmetric gas system into 22 identical lower-single-null L-mode discharges on DIII-D. The injection level was adjusted so that it did not significantly perturb the core or divertor plasmas, with a duration of similar to 3 s on each shot, for a total of similar to 300 T L of injected particles. The plasma shape remained very constant; the divertor strike points were controlled to similar to 1 cm at the divertor plate. At the beginning of the subsequent machine vent, 29 carbon tiles were removed for nuclear reaction analysis of C-13 content to determine regions of carbon deposition. It was found that only the tiles inboard of the inner strike point had appreciable 1 3 C above background. Visible spectroscopy measurements of the carbon injection and comparisons with modeling are consistent with carbon transport by means of scrape-off layer flow.
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