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1.	Albinsson, Sebastian, et al. (författare) Arterial remodeling and plasma volume expansion in caveolin-1 deficient mice. 2007 Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293, s. 1222-1231 Tidskriftsartikel (refereegranskat)abstract Caveolin- 1 ( Cav- 1) is essential for the morphology of membrane caveolae and exerts a negative influence on a number of signaling systems, including nitric oxide ( NO) production and activity of the MAP kinase cascade. In the vascular system, ablation of caveolin- 1 may thus be expected to cause arterial dilatation and increased vessel wall mass ( remodeling). This was tested in Cav- 1 knockout ( KO) mice by a detailed morphometric and functional analysis of mesenteric resistance arteries, shown to lack caveolae. Quantitative morphometry revealed increased media thickness and media- to- lumen ratio in KO. Pressure- induced myogenic tone and flow- induced dilatation were decreased in KO arteries, but both were increased toward wild- type ( WT) levels following NO synthase ( NOS) inhibition. Isometric force recordings following NOS inhibition showed rightward shifts of passive and active length- force relationships in KO, and the force response to alpha 1- adrenergic stimulation was increased. In contrast, media thickness and force response of the aorta were unaltered in KO vs. WT, whereas lumen diameter was increased. Mean arterial blood pressure during isoflurane anesthesia was not different in KO vs. WT, but greater fluctuation in blood pressure over time was noted. Following NOS inhibition, fluctuations disappeared and pressure increased twice as much in KO ( 38 +/- 6%) compared with WT ( 17 +/- 3%). Tracer- dilution experiments showed increased plasma volume in KO. We conclude that NO affects blood pressure more in Cav- 1 KO than in WT mice and that restructuring of resistance vessels and an increased responsiveness to adrenergic stimulation compensate for a decreased tone in Cav- 1 KO mice.
2.	Grände, Gustaf, et al. (författare) Unaltered Size-selectivity of the Glomerular Filtration Barrier in Caveolin-1 Knock-out (KO) mice. 2009 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 297:2, s. 257-262 Tidskriftsartikel (refereegranskat)abstract The transfer of albumin from blood to tissue has been found to be increased in caveolin-1 knock-out (KO) mice. This has been considered to reflect an increased microvascular permeability, conceivably caused by an increased endothelial production of nitric oxide (NO) in mice lacking caveolin-1. To investigate whether such an increase in endothelial NO-production would also affect the glomerular barrier characteristics, the glomerular sieving coefficients () to neutral, polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 (mol. radius 15-90 A) were determined in caveolin-1 KO mice vs. their wild-type counterparts. for Ficoll were assessed using high performance size exclusion chromatography (HPSEC) on blood and urine samples. Furthermore, the transcapillary escape rate (TER) of (125)I-labeled albumin and plasma volume (PV) were determined in both types of mice. Despite an increase in the glomerular filtration rate (GFR) in caveolin-1 KO mice (0.23+/-0.04 mL/min; n=7 vs. 0.10+/-0.02 mL/min; n=7; p<0.05) the glomerular Ficoll sieving curves were nearly identical. Furthermore, caveolin-1 KO mice showed an increased PV (6.59+/-0.42 mL/100g vs. 5.18+/-0.13 mL/100g; p<0.01) but only a tendency of an increased TER (14.69+/-1.59 %/h vs. 11.62+/-1.62 %/h; N.S.). It is concluded that in caveolin-1 KO mice the glomerular permeability was not increased, despite the presence of glomerular hyperfiltration. The present data are in line with the concept that the increased transvascular albumin leakage previously found in mice lacking caveolin-1 may be due to an elevation in systemic microvascular pressure following NO-induced precapillary vasodilatation, rather than being a consequence of an increased microvascular permeability per se. Key words: capillary permeability, nitric oxide, sieving coefficient, Ficoll, glomerular filtration rate.
3.	Rippe, Anna, et al. (författare) Disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in a mouse model of peritoneal dialysis (PD). 2007 Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 22:1, s. 88-95 Tidskriftsartikel (refereegranskat)abstract Background. This study was performed to establish a model for quantitative measurements of a number of basic peritoneal transport parameters, particularly transperitoneal clearances (Cl) of macromolecules, during mouse peritoneal dialysis. Methods. Mice were anaesthetized using 3% isofluorane inhalation anaesthesia. The right jugular vein and the left femoral artery were cannulated for infusion and sampling purposes and for registration of (mean) arterial blood pressure. Access to the peritoneal cavity occurred via a thin abdominal catheter (Ø 0.7 mm). About 2.5 ml of either 4% (n = 9) or 1.5% (n = 5) glucose containing PD-fluid were instilled intraperitoneally (i.p.). Dialysate volume was followed vs time using i.p. RISA (125I human serum albumin) as a volume marker, after correcting for RISA mass disappearance from the peritoneum, assessed separately (n = 11). Microsampling (10 µl) of plasma and dialysate was performed for determinations of glucose, haematocrit, radioactivity (RISA and 51Cr-EDTA) and Ficoll. Results. The i.p. volume vs time curves [VD(t)] were, after scaling, similar to those observed in humans (and in rats). Clearance of RISA out of the peritoneal cavity (Clout) was 9.33 ± 0.83 µl/min and the clearance of RISA to plasma (Cl->P) and the RISA clearance to the peritoneal cavity (Cl->D) were 1.49 ± 0.13 and 0.084 ± 0.008 µl/min, respectively. The peritoneal transport coefficients for 51Cr-EDTA and glucose, as well as Clout and Cl->P, were 13–17% of those previously assessed in 300 g rats, whereas Cl->D was only ~2% of that in rat. Conclusions. All peritoneal transport parameters measured, except Cl->D, scaled very well to the corresponding human data. The mechanisms of the disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in mice remain elusive and warrant further study.
4.	Rippe, Catarina, et al. (författare) Effects of glomerular filtration rate on Ficoll sieving coefficients (theta) in rats. 2006 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 69:8, s. 1326-1332 Tidskriftsartikel (refereegranskat)abstract The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients ( h) to neutral fluorescein isothiocyanate ( FITC)-Ficoll 70/400 obtained at low ( hydropenic) vs raised ( normal) glomerular filtration rates (GFRs). The h for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2 +/- 0.16 ml/ min (+/- s. e.), assessed using the plasma to urine clearance of FITC-inulin and Cr-51-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of similar to 2 ml/ min, 5 ml of serum together with glucagon ( 3 mu g/min) was given i.v. FITC- inulin and FITC- Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The h for Ficoll as a function of Stokes - Einstein radius was significantly reduced in the range of 13 - 43 angstrom when GFR was raised. The maximal h lowering effect, in relative terms, of raising GFR was obtained for a Ficoll a(e) of similar to 32 angstrom. For Ficoll(36 angstrom) (cf. albumin), h was reduced from 0.111 +/- 0.009 to 0.081 +/- 0.012 ( P<0.05; n = 7) for the GFR increment imposed. The reduction in h for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules <50 angstrom in radius.
5.	Rippe, Catarina, et al. (författare) Nature of glomerular capillary permeability changes following acute renal ischemia/reperfusion (I/R) injury in rats. 2006 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 291:6, s. 1362-1368 Tidskriftsartikel (refereegranskat)abstract This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (theta) were obtained by analyzing Ficoll [mol.radius (a(e)) 13-85 angstrom] in urine and plasma after 20 and 60 min I/R. Furthermore, theta for human serum albumin (HSA) was estimated using a tissue uptake technique after 20 and 60 min of I/R, while clearance of HSA compared with that for neutralized HSA (nHSA) was assessed after 20 min of I/R only. Glomerular filtration rate (GFR) was measured by [Cr-51] EDTA and inulin. I/R reduced GFR and increased theta for Ficoll molecules of a(e) > 55 angstrom and theta for albumin. theta for Ficoll vs. a(e), analysed using a two-pore model, demonstrated that, despite increases in theta, the large-pore fractional ultrafiltration coefficient (alpha(L)) was unchanged after 20 min of I/R, owing to the decline in GFR, but increased after 60 min of I/R. However, the apparent alpha(L) for albumin increased already after 20 min of I/R (P < 0.005) and the nHSA/HSA clearance ratio was slightly reduced, possibly reflecting a diminished negative charge barrier. In conclusion, after 20 min of I/R, indications of a reduced charge selectivity were noted, while after 60 min of I/R, there was mainly a reduction in size selectivity, compatible with an increased formation of large pores.
6.	Rippe, Catarina, et al. (författare) Size and charge selectivity of the glomerular filter in early experimental diabetes in rats 2007 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 293:5, s. 1533-1538 Tidskriftsartikel (refereegranskat)abstract Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 angstrom) were assessed using size exclusion chromatography. At 3 wk of diabetes, C1-HSA and C1-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of C1-HSA, whereas C1-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and C1-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores.
7.	Rosengren, Bert-Inge, et al. (författare) Transvascular protein transport in mice lacking endothelial caveolae. 2006 Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 291:3, s. 1371-1377 Tidskriftsartikel (refereegranskat)abstract Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO (n=12) and male control mice (n=13) were intubated and anesthetized using 2% isoflurane. I-125-labeled albumin, I-131-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and permeability-surface area product for glucose were assessed. Transvascular protein transport was higher in Cav-1-KO compared with control mice. Albumin clearance from plasma to peritoneum was 0.088 +/- 0.008 mu l/min in control and 0.179 +/- 0.012 mu l/min in Cav-1-KO (P = 0.001) mice. IgM clearance was 0.049 +/- 0.003 and 0.083 +/- 0.010 mu l/min in control and Cav-1-KO mice, respectively (P = 0.016). Ficoll clearance was increased in Cav-1-KO mice. In conclusion, the lack of caveolae in Cav-1-KO mice resulted in a marked increase in macromolecular transport. A two-pore analysis of the Ficoll clearance data revealed that the higher transport rate in Cav-1-KO mice was not compatible with the appearance of an alternative pathway for macromolecular transport. In contrast, the higher transperitoneal protein and Ficoll clearance is consistent with passive porous transport through an unperturbed two-pore system, presumably at an elevated capillary hydraulic pressure. Alternatively, the data may be explained by reductions in the selectivity of the endothelial glycocalyx, leading to an increased capillary hydraulic conductivity and large solute filtration.
8.	Asgeirsson, Daniel, et al. (författare) Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation. 2007 Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246 Tidskriftsartikel (refereegranskat)abstract Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
9.	Asgeirsson, Daniel, et al. (författare) Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats. 2006 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 291:5, s. 1083-1089 Tidskriftsartikel (refereegranskat)abstract It is established that the glomerular filter sieves macromolecules based on their size, shape, and charge. Anionic proteins are thus retarded compared with their neutral or cationic counterparts. However, recent studies have indicated that charge effects are small, or even "anomalous," for polysaccharides. We therefore investigated the impact of charge on the glomerular permeability to polysaccharides by comparing sieving coefficients ({theta}; primary urine-to-plasma concentration ratio) for negatively charged, carboxymethylated (CM) FITC-Ficoll and FITC-dextran with their neutral counterparts. For these probes, {theta} were determined in anesthetized Wistar rats [269 ± 2.7 g (±SE; n = 36)], whose ureters were cannulated for urine sampling. The glomerular filtration rate was assessed using FITC-inulin. Polysaccharides were constantly infused, and after equilibration, urine was collected and a midpoint plasma sample was taken. Size and concentration determinations of the FITC-labeled polysaccharides were achieved by size-exclusion HPLC (HPSEC). For CM-Ficoll, {theta} was significantly increased (32 times at 55 Å) compared with that of uncharged Ficoll. A small increase in {theta} for CM-dextran compared with neutral dextran was also observed (1.8 times at 55 Å). In conclusion, negatively charged Ficoll relative to neutral Ficoll was found to be markedly hyperpermeable across the glomerular filter. Furthermore, negatively charged Ficoll was observed to be larger on HPSEC compared with its neutral counterpart of the same molecular weight. It is proposed that the introduction of negative charges in the "dendrimeric," cross-linked Ficoll molecule may alter its configuration, so as to make it more extended, and conceivably, more flexible, thereby increasing its glomerular permeability. charge barrier; capillary permeability; macromolecules; fractional clearance; reflection coefficients IT IS GENERALLY ACCEPTED THAT the glomerular filter discriminates among macromolecules based on their size, shape, and net charge (6, 8). With respect to charge, the permeability of anionic dextran sulfate was found to be reduced and that of cationic, diethylaminoethyl (DEAE) dextran to be increased compared with that of neutral dextran (6). However, more recent studies have indicated that sulfated dextran may be processed in the kidney (28) and desulfated during its renal passage (10), and furthermore, that it may bind to plasma proteins (17), and to membrane phospholipids (25), causing an artifactual reduction in the sieving coefficients ({theta}; i.e., the primary urine-to-plasma concentration ratios) of dextran sulfate. In addition, isolated glomerular basement membranes (GBM) have generally failed to show charge selectivity when probed with neutral and negatively charged Ficoll (7) or native (anionic) or cationized albumin (4). In line with these findings, Schaeffer et al. (26) were unable to find (in rats in vivo) any difference between glomerular {theta} to carboxymethylated (non-sulfated) dextran or to hydroxymethyl starch (HES), both negatively charged, and their neutral counterparts. Furthermore, the HES molecules showed lower {theta} for any given Stokes-Einstein (SE) radius (cf. Ficoll) than did dextran. It was concluded that the glomerular filtration barrier restricts the transport of polysaccharide macromolecules as a function of size and configuration whereas the presence or absence of negative charge does not play any role. Further supporting these results, Guimarães et al. (18) did not find a decrease in glomerular permeability to negatively charged, carboxymethylated (CM) Ficoll compared with uncharged Ficoll, confirming a previous observation by Greive et al. (16). Instead, they found a markedly increased glomerular permeability to CM-Ficoll. In contrast to the apparent inability of the glomerular filter to discriminate between polysaccharides of different charge, there is ample evidence that, indeed, the glomerular filter selects globular proteins based on their charge. Thus anionic proteins are retarded compared with neutral and cationic proteins, as extensively reviewed by Comper and Glasgow (9) and Venturoli and Rippe (29). The reason the glomerular capillary wall exhibits low discrimination ability with respect to differently charged polysaccharides, while being able to separate proteins of different molecular charge, is obscure. However, one clue to this enigma could be the fact that carbohydrates exhibit an extended molecular configuration, with a larger SE radius, compared with that for globular proteins, for any given molecular mass (19, 29). Such an extended configuration, conceivably, generates a more flexible (compressible) structure and hence increases the molecule's permeability through the glomerular filtration barrier (29). Charge modification of a polysaccharide may lead to a further increase in molecular extension, favoring an increased flexibility and, thereby, an increased solute permeability. Could the process of charge modification of the highly cross linked and "ellipsoid" molecules of Ficoll (19) lead to conformational alterations, with increased molecular extension, increasing their permeability compared with their uncharged counterparts? If so, would the linear, "random coil," structure of dextran make it less affected by conformational changes, and thereby less hyperpermeable, when negatively charged? The present study was performed to test this hypothesis by comparing glomerular sieving coefficients to negatively charged, CM-Ficoll and -dextran vs. their uncharged molecular equivalents.
10.	Asgeirsson, Daniel, et al. (författare) Similitude of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane. 2009 Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 196:4, s. 427-433 Tidskriftsartikel (refereegranskat)abstract Abstract Aim: Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods: In anesthetized Wistar rats, FITC-Ficoll or FITC-pullulan together with (125)I-human serum albumin (RISA) or neutralized (125)I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis using conventional peritoneal dialysis fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analyzed with high performance size exclusion chromatography and a gamma counter, respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36-150 A, and for RISA and nBSA. Results: Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50+/-0.28 (muL/min; +/-SEM), tended to be lower than the clearances of Ficoll(36A) (6.55+/-0.25), pullulan(36A) (6.08+/-0.22) and nBSA (6.56+/-0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion: The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary-interstitial barrier.
11.	Axelsson, Josefin, et al. (författare) Acute hyperglycemia induces rapid, reversible increases of glomerular permeability in non-diabetic rats. 2010 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 298:6, s. 1306-1312 Tidskriftsartikel (refereegranskat)abstract This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anaesthetized Wistar rats (250-280g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (i.v.) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n=8); 2) hypertonic glucose as in 1) and a Rho-A-kinase inhibitor (Y-27632; Rho-G; n=8); 3) 20% mannitol (MANN; n=7), or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (picry) at ~320-325 mOsm/l (NaCl; n=8); 5) physiologic saline (SHAM; n=8). Fluorescein isothiocyanate (FITC)-Ficoll 70/400 was infused i.v. for at least 20 min before terminating the experiments, and plasma and urine collected to determine the glomerular sieving coefficients () for polydisperse Ficoll (mol. radius 15-80A) by high performance size exclusion chromatography. In G there was a marked increase in for Ficoll55-80A at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier be involved in these alterations. Key words: microalbuminuria, Rho-A-kinase, podocytes, endothelium.
12.	Axelsson, Josefin, et al. (författare) Effects of early endotoxemia and dextran-induced anaphylaxis on the size-selectivity of the glomerular filtration barrier in rats. 2009 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 296:2, s. 242-248 Tidskriftsartikel (refereegranskat)abstract This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anaesthetized Wistar rats, the left ureter was catheterized for urine collection, while simultaneously, blood access was achieved. Endotoxemia was induced by Lipopolysaccharide (LPS) from E. Coli, and glomerular permeability assessed at 60, 90 (ENDO-(60)/90; n=7) and 120 min (ENDO-120; n=7). Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min (ANA-5; n=8) and 40 min (ANA-40; n=9). Sham animals, were followed for either 5 or 120 min. The glomerular sieving coefficients () to FITC-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). 2 h after start of the LPS infusion, but not at 60 or 90 min, for Ficoll70A had increased markedly (from 2.91 x 10(-5) +/- 6.33 x 10(-6) to 7.78 x 10(-5) +/- 6.21 x 10(-6) (P<0.001)). In anaphylaxis there was a large increase in for Ficolls >60 A in mol. radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter. Key words: capillary permeability, Ficoll, sieving coefficient, albumin.
13.	Axelsson, Josefin, et al. (författare) Loss of size-selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma. 2009 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 297, s. 577-582 Tidskriftsartikel (refereegranskat)abstract Post-traumatic microalbuminuria may be caused by either charge- or size-selective alterations in the glomerular filtration barrier, or both, and/or to a reduction in proximal tubular protein reabsorption (PTR). This study was performed to elucidate the pathophysiology of the increases in glomerular permeability occurring in rats exposed to laparotomy or to laparotomy and muscle trauma. In anaesthetized Wistar rats (250-280 g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats were exposed to trauma by laparotomy (L) (n=8), or by a combination of L and muscle trauma (MT), induced by topical blunt injury of the abdominal muscles bilaterally. After L muscles were crushed using a hemostatic forceps at either 2x2 sites ("small" MT; n=9), or at 2x5 sites ("large" MT; n=9). Sham groups (n=16), not exposed to laparotomy, were used as controls. The glomerular sieving coefficients () to polydisperse, fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 13-80A) were determined at 5 or 60 min after L and (L + MT), respectively, from plasma and urine samples, and analyzed by high performance size-exclusion chromatography (HPSEC). A tissue uptake technique was used to assess for (125)I-serum albumin. L, with or without MT, increased for Ficoll55-80A and albumin rapidly and markedly. -Ficoll70A thus increased approximately threefold, and for albumin significantly, for all trauma groups. According to the "two-pore model" of glomerular permeability these changes reflect an increase in the number of large pores in the glomerular filter without any primary changes in the charge-selective properties of the filter. Key words: microalbuminuria, glomerular sieving coefficients, albumin, Ficoll.
14.	Axelsson, Josefin, et al. (författare) mTOR inhibition with temsirolimus causes acute increases in glomerular permeability, but inhibits the dynamic permeability actions of puromycin aminonucleoside. 2015 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 308:10, s. 1056-1064 Tidskriftsartikel (refereegranskat)abstract Inhibitors of the mammalian target of rapamycin (mTORi) can produce de novo proteinuria in kidney transplant patients. On the other hand, mTORi has been shown to suppress disease progression in several animal models of kidney disease. In the present study we investigated whether glomerular permeability can be acutely altered by the mTORi, temsirolimus, and whether mTORi can affect acute purumycin aminonucleoside (PAN) or angiotensin II (AngII) induced glomerular hyperpermeability. In anaesthetized Wistar rats, the left ureter was cannulated for urine collection, while simultaneously, blood access was achieved. Temsirolimus was administered as a single dose i.v. 30 min before the start of the experiments in animals infused with PAN or AngII or in non-exposed animals. Polydispersed FITC-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA infusion was given during the whole experiment. Measurements of Ficoll in plasma and urine were performed sequentially before the temsirolimus injection (baseline) and at 5, 15, 30, 60 and 120 min after the start of the experiments. Urine and plasma samples were analyzed by high performance size exclusion chromatography (HPSEC) to assess glomerular sieving coefficients (θ) for Ficoll10-80Å. Temsirolimus per se increased baseline glomerular permeability to Ficoll50-80Å 45 min after its administration, a ROS dependent phenomenon. PAN caused a rapid and reversible increase in glomerular permeability, peaking at 5 min, and again at 60-120 min, which could be blocked by the ROS scavenger, tempol. mTORi abrogated the second permeability peak induced by PAN. However, it had no effect on the immediate AngII or PAN induced increases in glomerular permeability.
15.	Axelsson, Josefin, et al. (författare) Rapid, dynamic changes in glomerular permeability to macromolecules during systemic Angiotensin II (AngII) infusion in rats. 2012 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 303:6, s. 790-799 Tidskriftsartikel (refereegranskat)abstract The actions of systemic angiotensin II (AngII) infusions on glomerular permeability were investigated in vivo. In anaesthetized Wistar rats (250-280g) the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused i.v. with either of four doses of AngII (16 ng/kg/min (Lo-AngII; n=7), 230 ng/kg/min (Lo-Int-AngII; n=8), 910 ng/kg/min (Hi-Int-AngII; n=7), or 1.82 μg/kg/min (Hi-AngII; n=8)), or with the calcium channel blocker, nimodipine, together with the Hi-Int-AngII dose (n=6), respectively, and with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60 and 120 min and analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. In AngII groups there was a rapid, marked increase in glomerular permeability (θ) to Ficoll molecules >34Å, which was completely abrogated by the AngII-blocker, candesartan. The permeability increase was reversible within 15-60 min, but some increases remained even after 60 min. For the highest AngII doses given GFR decreased transiently, concomitant with marked increases in MAP. Nimodipine blocked the hemodynamic AngII actions, whereas the glomerular permeability response remained unchanged. According to a two-pore model and a log-normal distributed pore model the AngII induced increases in glomerular permeability are compatible with an increased number of "large pores" in the glomerular filter, and, to some extent, an increase in the dispersity of the small pore radius.
16.	Axelsson, Josefin, et al. (författare) Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo 2011 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 301:4, s. 708-712 Tidskriftsartikel (refereegranskat)abstract Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B. Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo. Am J Physiol Renal Physiol 301: F708-F712, 2011. First published July 20, 2011; doi:10.1152/ajprenal.00183.2011.-The glomerular filtration barrier (GFB) is commonly conceived as a negatively charged sieve to proteins. Recent studies, however, indicate that glomerular charge effects are small for anionic, carboxymethylated (CM) dextran vs. neutral dextran. Furthermore, two studies assessing the glomerular sieving coefficients (theta) for negative CM-Ficoll vs. native Ficoll have demonstrated an increased glomerular permeability for CM-Ficoll (Asgeirsson D, Venturoli D, Rippe B, Rippe C. Am J Physiol Renal Physiol 291: F1083-F1089, 2006; Guimaraes M, Nikolovski J, Pratt L, Greive K, Comper W. Am Physiol Renal Physiol 285: F1118-F1124, 2003.). The CM-Ficoll used, however, showed a larger Stokes-Einstein radius (a(e)) than neutral Ficoll, and it was proposed that the introduction of negative charges in the Ficoll molecule had made it more flexible and permeable. Recently, a negative FITC-labeled CM-Ficoll (CMI-Ficoll) was produced with a conformation identical to that of neutral FITC-Ficoll. Using these probes, we determined their theta:s in anesthetized Wistar rats (259 +/- 2.5 g). After blood access had been achieved, the left ureter was cannulated for urine sampling. Either polysaccharide was infused (iv) together with a filtration marker, and urine and plasma were collected. Assessment of theta FITC-Ficoll was achieved by high-performance size-exclusion chromatography (HPSEC). CMI-Ficoll and native Ficoll had identical elugrams on the HPSEC. Diffusion of anionic Ficoll was significantly reduced compared with that of neutral Ficoll across the GFB for molecules of a(e) similar to 20-35 angstrom, while there were no charge effects for Ficoll of a(e) similar to 35-80 angstrom. The data are consistent with a charge effect present in "small pores," but not in "large pores," of the GFB and mimicked those obtained for anionic membranes in vitro for the same probes.
17.	Axelsson, Josefin, et al. (författare) Scavengers of reactive oxygen species, paracalcitol, RhoA and Rac-1 inhibitors and tacrolimus inhibit angiotensin II induced actions on glomerular permeability. 2013 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 305:3, s. 237-243 Tidskriftsartikel (refereegranskat)abstract Systemic infusions of angiotensin II (AngII) rapidly induce large, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor(s), AngII generates reactive oxygen species (ROS) and produces Ca(2+) influx into cells, leading to activation of a plethora of signaling cascades, including e.g. calcineurin, and small GTPases, such as Rac-1 and RhoA. In the present study we sought to interact with some of these cascades in order to test potential novel antiproteinuric agents. In anaesthetized Wistar rats the left urether was cannulated for urine collection, and blood access was achieved. Rats were infused with AngII (16 ng/kg/min) alone, or together with the ROS scavengers, TEMPOL or dimethylthiourea (DMTU), or the D-vitamin analog, paracalcitol, the RhoA-kinase inhibitor, Y-27632, the Rac-1 inhibitor, NSC-23766, or the calcineurin inhibitor, tacrolimus. FITC-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA were infused throughout the experiment. Plasma and urine samples were taken during baseline and at 5 and 15 min after the start of the infusions and analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ) for Ficoll10-80Å. AngII infusion into rats caused marked increases in glomerular permeability to large Ficoll molecules (Ficoll50-80Å), which were abrogated by the ROS scavenger TEMPOL and partly by DMTU. Paracalcitol, RhoA and Rac-1 inhibition, and, to some extent, tacrolimus, but not prostacyclin, could also inhibit the glomerular permeability actions of AngII. Our data suggest that cellular ROS generation and active Ca(2+) signaling are involved in AngII induced increases in glomerular permeability.
18.	Axelsson, Josefin, et al. (författare) Size-selectivity of a synthetic high-flux and a high cut-off dialyzing membrane compared to that of the rat glomerular filtration barrier 2012 Ingår i: Journal of Membrane Science. - : Elsevier BV. - 0376-7388. ; 413, s. 29-37 Tidskriftsartikel (refereegranskat)abstract The aim of the present study was to investigate the size-selectivity of two different synthetic dialyzing membranes, having widely differing sieving properties, with respect to their handling of polydispersed fluorescein isothiocyanate (FITC)-Ficoll, FITC-dextran and of proteins, i.e. I-125-human serum albumin (RISA) and I-125-myoglobin (Myo). Are Ficoll and dextran, compared to proteins, "hyperpermeable" across synthetic dialyzing membranes, similar to their behavior across the glomerular filtration barrier (GFB)? A high-flux membrane (HF-Revaclear (R); n = 12) and a high cut-off membrane (HCO; n = 14) in capillary mini-dialyzers were perfused with diluted horse serum. The perfusate contained polydisperse FITC-Ficoll 70/400 or FITC-dextran (mol radius 13-80 angstrom), FITC-Inulin, and, in some experiments, RISA/Myo. After a priming period, sampling of filtrate occurred, and a midpoint plasma sample taken. Filtrate-to-plasma concentration ratios (theta) vs. molecular radius (a(e)) were assessed using HPLC for Ficoll and dextran. Size-selectivity for Ficoll increased in the order: HF-Revaclear (R) < rat glomerulus < HCO. Although the HCO filter showed the highest cut-off, this occurred at the expense of a high permeability to albumin and large Ficoll molecules and a high degree of dispersity of (small) pore radii, as assessed using a log-normal + shunt distributed pore model. According to a two-pore model, the fractional hydraulic conductance accounted for by large pores (alpha(L)) was 8.58 +/- 0.93 x 10(-3) and 1.51 +/- 0.88 x 10(-3) for the HCO and the HF-Revaclear (R), respectively, compared to 4.1 +/- 0.80 x 10(-5) for the rat glomerulus. In conclusion, the HCO filter investigated showed a high theta for myoglobin, similar to that of the GFB. However, the number of large pores was markedly higher and the pore size heterogeneity markedly larger than for the GFB. Membrane permeability was dependent on molecular species and increased in the order: proteins < Ficoll < dextran. (C) 2012 Published by Elsevier B.V.
19.	Axelsson, Josefin, et al. (författare) Transient and sustained increases in glomerular permeability following ANP infusion in rats. 2011 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 300, s. 24-30 Tidskriftsartikel (refereegranskat)abstract The present study was performed to investigate the effects of systemic atrial natriuretic peptide (ANP) infusion on the glomerular permeability to macromolecules in rats. In anaesthetized Wistar rats (250-280g) the left urether was cannulated for urine collection while simultaneously blood access was achieved. Rats were continuously infused i.v. with ANP, 30 ng/min/kg (Lo-ANP; n=8) or 800 ng/min/kg (Hi-ANP; n=10) or 0.9% NaCl (SHAM; n=16), respectively, and with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 13-90Å) and (51)Cr-EDTA for 2 h. Plasma and urine samples were taken at 5, 15, 30, 60 and 120 min of ANP infusion, and analyzed by high performance size exclusion chromatography (HPLC) for determination of glomerular sieving coefficients () for Ficoll. GFR was also assessed ((51)Cr-EDTA). In Hi-ANP there was a rapid (within 5 min), but bimodal, increase in glomerular permeability. to high MW Ficoll thus reached a maximum at 15 min, after which returned to near control at 30 min, to again increase moderately at 60 and 120 min. In Lo-ANP there was also a rapid, reversible increase in glomerular , returning to near control at 30 min, followed by just a tendency of a sustained increase in permeability, but with a significant increase in "large pore" radius. In conclusion, in Hi-ANP there was a rapid increase in glomerular permeability, with an early, partly reversible permeability peak, followed by a (moderate) sustained increase in permeability. In Lo-ANP animals, only the initial permeability peak was evident. In both Lo-ANP and Hi-ANP the glomerular sieving pattern observed was found to mainly reflect an increase in the number and radius of "large pores" in the glomerular filter.
20.	Dolinina, Julia, et al. (författare) Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species 2016 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 311:5, s. 984-990 Tidskriftsartikel (refereegranskat)abstract There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with eitherL-NAME orL-NAME together with the superoxide scavenger Tempol, or together withL-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h.L-NAME increased θ for Ficoll70Å from 2.27 ± 1.30 ˟ 10-5 to 8.46 ± 2.06 ˟ 10-5 (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed withL-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo byL-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.
21.	Karpman, Diana, et al. (författare) NT-rådets ställningstagande till eculizumab är oacceptabelt 2015 Ingår i: Läkartidningen. - Stockholm : Läkartidningen Förlag AB. - 1652-7518 .- 0023-7205. ; 112 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
22.	Karpman, Diana, et al. (författare) Slutreplik, Diana Karpman och medförfattare : - NT-rådet bör omedelbart återkalla sitt beslut om eculizumab 2015 Ingår i: Läkartidningen. - 1652-7518. ; 112 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	Krawczyk, Katarzyna K., et al. (författare) Assessing the contribution of thrombospondin-4 induction and ATF6α activation to endoplasmic reticulum expansion and phenotypic modulation in bladder outlet obstruction 2016 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Tidskriftsartikel (refereegranskat)abstract Phenotypic modulation of smooth muscle cells is a hallmark of disease. The associated expansion of endoplasmic reticulum (ER) volume remains unexplained. Thrombospondin-4 was recently found to promote ATF6α activation leading to ER expansion. Using bladder outlet obstruction as a paradigm for phenotypic modulation, we tested if thrombospondin-4 is induced in association with ATF6α activation and ER expansion. Thrombospondin-4 was induced and ATF6α was activated after outlet obstruction in rodents. Increased abundance of spliced of Xbp1, another ER-stress sensor, and induction of Atf4 and Creb3l2 was also seen. Downstream of ATF6α, Calr, Manf, Sdf2l1 and Pdi increased as did ER size, whereas contractile markers were reduced. Overexpression of ATF6α, but not of thrombospondin-4, increased Calr, Manf, Sdf2l1 and Pdi and caused ER expansion, but the contractile markers were inert. Knockout of thrombospondin-4 neither affected bladder growth nor expression of ATF6α target genes, and repression of contractile markers was the same, even if ATF6α activation was curtailed. Increases of Xbp1s, Atf4 and Creb3l2 were similar. Our findings demonstrate reciprocal regulation of the unfolded protein response, including ATF6α activation and ER expansion, and reduced contractile differentiation in bladder outlet obstruction occurring independently of thrombospondin-4, which however is a sensitive indicator of obstruction.
24.	Lund, Ulla, et al. (författare) Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys 2003 Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 284:6, s. 1226-1234 Tidskriftsartikel (refereegranskat)abstract The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs. glomerular filtration rate (GFR; Cr-51-EDTA clearance) in intact rats for radiolabeled myoglobin, kappa-dimer, neutral horseradish peroxidase (nHRP), neutral human serum albumin (nHSA), and native albumin (HSA). To obtain theta, glomerular tracer clearance, assessed from the 7- to 8-min kidney uptake of protein, was divided by the GFR. The data were fitted with a two-pore model of glomerular permeability, where the small-pore radius was 37.35 +/- 1.11(SE) Angstrom, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 . 10(6) cm. Although seemingly horizontal for nHRP and nHSA, the log theta vs. GFR curves showed slightly negative slopes for the proteins investigated in the GFR interval of 2-4.5 ml/min. Strong negative ( linear) correlations between ( log) theta and GFR were obtained for myoglobin (P = 0.002) and HSA (P = 0.006), whereas they were relatively weak for nHRP and nHSA and nonsignificant for kappa-dimer. theta for nHSA was markedly higher than that for HSA. In conclusion, there were no indications of increases in theta vs. GFR, as indicative of concentration polarization, for the proteins investigated at high GFRs. Furthermore, the glomerular small-pore radius assessed from endogenous (neutral) protein sieving data was found to be smaller than previously determined using dextran or Ficoll as test molecules.
25.	Morelle, Johann, et al. (författare) Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane 2018 Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 29:7, s. 1875-1886 Tidskriftsartikel (refereegranskat)abstract Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.
26.	Musi, Barbara, et al. (författare) VEGF-induced mesenteric neoangiogenesis caused increases in peritoneal transport in shaken, but not unshaken, rats. 2004 Ingår i: 1st Joint ISpd/EuroPD congress on peritoneal Dialysis, Amsterdam, The Netherlands, 040827-040831. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
27.	Ni, J, et al. (författare) Aquaporin-1 plays an essential role in water permeability and ultrafiltration during peritoneal dialysis 2006 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 69:9, s. 1518-1525 Tidskriftsartikel (refereegranskat)abstract The water channel aquaporin-1 (AQP1) is considered as the molecular counterpart of the ultrasmall pore predicted by the three-pore model of fluid transport across the peritoneal membrane. However, the definitive proof of the implication of AQP1 in solute-free water transport, sodium sieving, and ultrafiltration (UF) during peritoneal dialysis (PD) is lacking, and the effects of its deletion on the structure of the membrane are unknown. Using real-time reverse transcriptase-polymerase chain reaction and immunogold electron microscopy, we showed that AQP1 is the most abundant member of the AQP gene family expressed in the mouse peritoneum, and the only one located in the capillary endothelium. Transport studies during a 2-h dwell demonstrated that, in comparison with Aqp1(+/+) littermates, Aqp1(-/-) mice had no sodium sieving; an B70% decrease in the initial, solute-free UF; and an B50% decrease in cumulative UF. These modifications occurred despite unchanged osmotic gradient and transport of small solutes in the Aqp1(-/-) mice. Heterozygous Aqp1(+/-) mice showed intermediate values in sodium sieving and initial UF, whereas cumulative UF was similar to Aqp1(+/+) mice. The deletion of AQP1 had no effect on the expression of other AQPs and on the density, structure, or diameter of peritoneal capillaries. These data provide direct evidence for the role of AQP1 during PD. They validate essential predictions of the three-pore model: (i) the ultrasmall pores account for the sodium sieving, and (ii) they mediate 50% of UF during a hypertonic dwell.
28.	Segelmark, Mårten, et al. (författare) NT-rådet bör omedelbart återkalla sitt beslut om eculizumab 2015 Ingår i: Läkartidningen. - Stockholm : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 112 Tidskriftsartikel (populärvet., debatt m.m.)
29.	Sverrisson, Kristinn, et al. (författare) Acute, Reactive Oxygen Species (ROS) dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo. 2015 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 309:9, s. 800-806 Tidskriftsartikel (refereegranskat)abstract This study was performed in order to investigate the immediate actions of the proinflammatory cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anaesthetized rats blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused i.v. with either IL-1β (0.4 and 2 μg·kg(-1)·h(-1)), TNF-α (0.4 and 2 μg·kg(-1)·h(-1)) or IL-6 (4 and 8 μg·kg(-1)·h(-1)), together with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 and Inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed ((51)Cr-EDTA). In separate experiments the superoxide scavenger, tempol (30 mg·kg(-1)·h(-1)), was given before and during cytokine infusions. IL-1β and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50-80Å), peaking at 5-30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1β, TNF-α and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger, tempol, suggesting an important role of ROS in acute cytokine induced permeability changes of the GFB.
30.	Sverrisson, Kristinn, et al. (författare) Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo. 2014 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 307:10, s. 1136-1143 Tidskriftsartikel (refereegranskat)abstract The proteinuric actions of protamine sulfate (PS) have classically been, at least partly, attributed to alterations of the negatively charged glomerular endothelial glycocalyx (GC). To investigate whether the charge-selective properties of the glomerular filtration barrier (GFB) would be altered by PS we assessed the glomerular sieving of conventional, uncharged, polydispersed Ficoll (n-Ficoll) compared to charge modified, conformationally intact, anionic (carboxymethylated) Ficoll (a-Ficoll) before and after systemic infusions of PS in rats. For comparison we also investigated the impact of hyaluronidase (Hyase), which partially degrades the GC, on GFB permeability. In anaesthetized Wistar rats blood access was achieved and the left ureter was cannulated for urine collection. Rats were infused with either n-Ficoll or a-Ficoll before and during systemic infusions with either PS or Hyase. Plasma and urine samples were taken repeatedly and analyzed by high performance size exclusion chromatography (HPSEC) for assessing glomerular sieving coefficients (θ) for Ficoll (radius 10-80Å). The GFB showed a significant glomerular charge selectivity for Ficoll molecules of radius 20-35Å (Ficoll20-35Å). PS and Hyase infusions reversibly increased θ for large Ficoll molecules (Ficoll50-80Å). Thus, for PS θ for a-Ficoll70Å increased from 2.47 x 10(-5) ± 1.1(-5) to 7.25 x 10(-5) ± 1.1(-5) (P<0.05) at 15 min. For Hyase the changes in a-Ficoll50-80Å were, however, not statistically significant. Neither PS nor Hyase had any effect on θ for n-Ficoll20-45Å or a-Ficoll20-45Å. It is concluded that systemically administered PS and Hyase in moderate doses dynamically decreased the size-selectivity of the rat GFB without affecting its charge selective properties.
31.	Sverrisson, Kristinn, et al. (författare) Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with alfa-1-microglobulin and tempol 2014 Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 306:4, s. 442-448 Tidskriftsartikel (refereegranskat)abstract Extracellular fetal hemoglobin (HbF) and adult hemoglobin (HbA) are proinflammatory and generate ROS. Increased plasma levels of extracellular HbF have recently been reported to occur in early preeclampsia. α1-Microglobulin (A1M) is a physiological heme-binding protein and radical scavenger that has been shown to counteract vascular permeability increases induced by HbA in the perfused placenta. The present study was performed to investigate whether HbF and HbA will increase glomerular permeability in vivo and to test whether A1M and tempol, a ROS scavenger, can prevent their effects. Anesthetized Wistar rats were continuously infused intravenously with either HbA, HbF, or cyano-inactivated HbF together with FITC-Ficoll-70/400, inulin, and51Cr-labeled EDTA for 2 h. Plasma samples and urine samples (left ureter) were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients for Ficoll of radius 10–80 Å. In separate experiments, A1M or tempol was given before and during Hb infusions. Extracellular HbF caused rapid, transient increases in glomerular permeability to large Ficoll molecules (50–80Å), contrary to the effects of HbA and cyano-inactivated HbF. For HbF, glomerular sieving coefficients for Ficoll of radius 60Å increased from 3.85 ± 0.85 × 10−5to 2.60 ± 0.96 × 10−4at 15 min, changes that were abrogated by tempol and reduced by A1M. In conclusion, our data demonstrate that extracellular HbF, infused systemically, can acutely increase glomerular permeability through inducing oxidative stress.
32.	Akaberi, Shahriar, et al. (författare) Temporal trends and risk factors for parathyroidectomy in the Swedish dialysis and transplant population - a nationwide, population-based study 1991 - 2009. 2014 Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 15:May 8 Tidskriftsartikel (refereegranskat)abstract Many patients on renal replacement therapy (RRT) require parathyroidectomy (PTX). Trends and current rates of PTX on a national level are not known. Furthermore, it is not completely clear which factors influence rates of PTX. Thus, our aim was to investigate the incidence, regional distribution and factors associated with PTX as well as possible temporal changes, in the Swedish RRT population.
33.	Bakoush, Omran, et al. (författare) High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases 2001 Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:7, s. 1357-1363 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.
34.	Bakoush, Omran, et al. (författare) Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy. 2002 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 61:1, s. 203-208 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall.
35.	Bakoush, Omran, et al. (författare) Inaccuracy of GFR predictions by plasma cystatin C in patients without kidney dysfunction and in advanced kidney disease. 2008 Ingår i: Clinical Nephrology. - 0301-0430. ; 69:5, s. 331-338 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In clinical practice there is need for a simple and reliable test for determination of impaired renal function. With reductions in GFR, the plasma cystatin C concentration (C, mg/l) will increase earlier than serum creatinine, and it is generally agreed that plasma cystatin C is only little affected by body weight, age or sex. However, some reports indicate that cystatin C may be influenced not only by GFR, but also by malignancy, inflammation and high doses of corticosteroids. The aim of the present study was to investigate how plasma cystatin C predicts GFR in distinct subcategories of patients with various disorders as well as in organ transplant patients. METHODS: Plasma cystatin C was measured in 536 patients (age range 0.3-96 years, 262 females, 274 males), consecutively referred to our hospital for determination of GFR by iohexol clearance. Correlations of log GFR vs. log cystatin C were used to compare plasma cystatin C and measured GFR for the following categories: individuals with no known kidney disease (No-KD), malignant patients with (mostly) normal GFR, solid organ-transplanted patients, and patients with native chronic kidney disease (CKD). RESULTS: In patients with normal kidney function and cystatin C level GFR>30 ml/min(-1) (1.73 m2)(-1)) or solid organ transplantation (GFR=84.55 C(1.7666) and GFR=83.95(C-1.5968), respectively). CONCLUSION: Therefore, for these categories, a common equation for all patients with increased cystatin C, irrespective of cause of renal impairment, could be used, namely that presented by Grubb et al. [2005] (GFR=83.93(C-1.676)). However, at marked reductions of renal function (GFR<30 or cystatin C>2), i.e. for CKD Stages 4 and 5, the Grubb prediction equation is less accurate. Based on our data, we suggest the equation GFR=50.52 C(-1.26) for this category of patients.
36.	Bakoush, Omran, et al. (författare) Increased glomerular albumin permeability in old spontaneously hypertensive rats. 2004 Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 19:7, s. 1724-1731 Tidskriftsartikel (refereegranskat)
37.	Bakoush, Omran, et al. (författare) Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM excretion but not to the changes in the degree of albuminuria. 2003 Ingår i: Clinical Nephrology. - 0301-0430. ; 59:5, s. 345-352 Tidskriftsartikel (refereegranskat)
38.	Bakoush, Omran, et al. (författare) Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria 2001 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 60:5, s. 1904-1909 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Proteinuric glomerular diseases often are associated with tubulointerstitial injury, which imposes on the progression of renal failure. Tubular damage is partly referable to toxic effects on the tubular epithelial cells induced by filtered plasma proteins. Patients with nonselective proteinuria, that is, increased urine excretion of high-molecular-weight plasma proteins such as IgG in comparison to albumin, often have poor renal outcome. The present observational study examined correlations between the degree of tubular damage, measured by urine concentration of protein HC, and the levels of urine IgG and albuminuria. METHODS: Measurements of urine concentrations of IgG, albumin, and protein HC were performed in 56 proteinuric patients (33 males and 23 females) with nondiabetic glomerular diseases at the time of the diagnostic renal biopsy and at a mean of 49 follow-up months. RESULTS: A highly significant correlation between the urine IgG excretion and the urine protein HC concentration was found both at the start and at the end of the observational time (r = 0.74 and 0.65, respectively, P < 0.001). Furthermore, alterations in the urinary excretion of the two proteins in single patients correlated significantly to each other (r = 0.84, P < 0.001). The correlation between the degree of albuminuria and the protein HC excretion was significant at the time of kidney biopsy, but ceased to exist during the follow-up time. Stepwise linear regression analysis showed that in comparison with the creatinine clearance and albuminuria, only the changes in urinary IgG excretion were related to the corresponding changes in urinary protein HC excretion (r = 0.84 and r2 = 0.7, P < 0.001). CONCLUSION: The findings of the study suggest that the urinary protein HC concentration correlates to the degree of IgG-uria but not to the degree of albuminuria during the course of proteinuric glomerular disease. Whether this correlation is to be explained by an intrinsic toxic effect on tubular cells executed by IgG or perhaps by some other high molecular weight proteins, needs to be investigated further. However, the results contribute to the understanding of the poor renal survival in patients with glomerular diseases and nonselective proteinuria.
39.	Bankell, Elisabeth, et al. (författare) Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1 2024 Ingår i: Scientific Reports. - 2045-2322. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Myocardin-related transcription factors (MRTFs: myocardin/MYOCD, MRTF-A/MRTFA, and MRTF-B/MRTFB) suppress production of pro-inflammatory cytokines and chemokines in human smooth muscle cells (SMCs) through sequestration of RelA in the NF-κB complex, but additional mechanisms are likely involved. The cGAS-STING pathway is activated by double-stranded DNA in the cytosolic compartment and acts through TANK-binding kinase 1 (TBK1) to spark inflammation. The present study tested if MRTFs suppress inflammation also by targeting cGAS-STING signaling. Interrogation of a transcriptomic dataset where myocardin was overexpressed using a panel of 56 cGAS-STING cytokines showed the panel to be repressed. Moreover, MYOCD, MRTFA, and SRF associated negatively with the panel in human arteries. RT-qPCR in human bronchial SMCs showed that all MRTFs reduced pro-inflammatory cytokines on the panel. MRTFs diminished phosphorylation of TBK1, while STING phosphorylation was marginally affected. The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A. Co-immunoprecipitation and proximity ligation assays supported binding between MRTF-A and TBK1 in SMCs. MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease.
40.	Bertilsson, Sara, et al. (författare) Microproteinuria Predicts Organ Failure in Patients Presenting with Acute Pancreatitis 2016 Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:12, s. 3592-3601 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: The disease course of acute pancreatitis (AP) ranges from mild and self-limiting to severe inflammation, associated with significant morbidity and mortality. At present, there are no universally accepted and reliable predictors for severity. Microproteinuria has been associated with the presence of systemic inflammatory response syndrome as well as trauma, although its association with AP is not well understood. The aim of this study was to investigate the value of microproteinuria to predict development of organ failure in AP.METHODS: Consecutive AP patients were prospectively enrolled. Urine samples were collected upon admission, 12-24 h after admission, and 3 months post-discharge for calculation of urine α1-microglobulin-, albumin-, IgG-, and IgM/creatinine ratios. Data regarding AP etiology, severity, and development of organ failure were registered.RESULTS: Overall, 92 AP patients were included (14 % with organ failure; 6 % with severe AP). The α1-microglobulin-, albumin-, and IgG/creatinine ratios correlated with high-sensitivity C-reactive protein 48 h after admission (r = 0.47-0.61, p < 0.001 for all). They were also significantly higher in patients with versus without organ failure (p < 0.05 for all). The α1-microglobulin/creatinine ratio upon admission predicted organ failure [adjusted odds ratio 1.286, 95 % confidence interval (CI) 1.024-1.614] with similar accuracy (AUROC 0.81, 95 % CI 0.69-0.94) as the more complex APACHE II score (AUROC 0.86, 95 % CI 0.70-1.00).CONCLUSION: The α1-microglobulin/creatinine ratio upon presentation with AP is related to inflammation and predicts development of organ failure. Further studies are warranted to evaluate its potential usefulness in predicting outcome for AP patients.
41.	Carlsson, Ola, et al. (författare) In vivo inhibition of transcellular water channels (Aquaporin-1) during acute peritoneal dialysis in rats 1996 Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 1522-1539. ; 271, s. 2254-2262 Tidskriftsartikel (refereegranskat)abstract During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.
42.	Christensen, El, et al. (författare) Controversies in nephrology: renal albumin handling, facts, and artifacts! 2007 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 72:10, s. 1192-1194 Forskningsöversikt (refereegranskat)abstract In this article, we discuss and contradict a recent publication by Russo et al., which suggests that the filtration of large amounts of albumin followed by transtubular transport of intact albumin is a physiological phenomenon.
43.	Clyne, Naomi, et al. (författare) Akut njurskada 2015. - 1:1 Ingår i: Njursjukdom : Teori och Klinik - Teori och Klinik. - 9789144089256 ; , s. 245-263 Bokkapitel (populärvet., debatt m.m.)
44.	Clyne, Naomi, et al. (författare) Att bli njursjuk och sköta sin behandling 2015. - 1.1 Ingår i: Njursjukdom : Teori och klinik - Teori och klinik. - 9789144089256 ; , s. 379-382 Bokkapitel (populärvet., debatt m.m.)
45.	Clyne, Naomi, et al. (författare) Fysisk träning 2015. - 1.1 Ingår i: Njursjukdom : Teori och klinik - Teori och klinik. - 9789144089256 ; , s. 393-400 Bokkapitel (populärvet., debatt m.m.)
46.	Clyne, Naomi, et al. (författare) Läkaren och vårdens organisation 2015. - 1.1 Ingår i: Njursjukdom : Teori och klinik - Teori och klinik. - 9789144089256 ; , s. 369-378 Bokkapitel (populärvet., debatt m.m.)
47.	Clyne, Naomi, et al. (författare) Preventiv nefrologi 2015. - 1:1 Ingår i: Njursjukdom : Teori och klinik - Teori och klinik. - 9789144089256 ; , s. 363-368 Bokkapitel (populärvet., debatt m.m.)
48.	Dahl, Sara, et al. (författare) Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells 2020 Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 69:6, s. 579-588 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells.MATERIALS AND METHODS: Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA.RESULTS: LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function.CONCLUSIONS: LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.
49.	Davies, Simon, et al. (författare) The effects of low-sodium peritoneal dialysis fluids on blood pressure, thirst and volume status 2009 Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 24:5, s. 1609-1617 Tidskriftsartikel (refereegranskat)abstract Background. Poor ultrafiltration is associated with worse outcomes in peritoneal dialysis (PD) patients. This might in part reflect problems associated with salt and water excess. Increasing the diffusive component of peritoneal sodium removal using low-sodium PD fluids might have beneficial effects on blood pressure (BP), thirst and fluid status that could translate into clinical benefits. Methods. Using a multicentre, prospective, baseline controlled (1 month), non-randomized intervention (2 months) design, two novel solutions designed from predictions using the three-pore model were investigated. In group A ([Na+] = 115 mmol/l), the glucose (G) was increased to 2.0% to compensate for reduced osmolality whereas in group B ([Na+] = 102 mmol/l), it was unchanged (2.5%). Both solutions were substituted for one 3- to 5-h exchange per day and no change was made to the rest of the dialysis regime. Results. Ten patients in group A and 15 in group B completed the study. Both solutions resulted in significant increases (30-50 mmol/dwell) in diffusive sodium removal during the test exchanges, P < 0.001. Ultrafiltration was maintained in group A but reduced in group B. Ambulatory nocturnal mean BP fell in group A [93.1 +/- 10.6 mmHg (+/- SD) versus 85.1 +/- 10.2 mmHg, P < 0.05], but was stable in group B (95.4 +/- 9.4 versus 95.1.1 +/- 10.7 mmHg, NS). Thirst reduced independent of appetite and mood in both groups by 2 months, more markedly in group A. Indices of fluid status, including TBW by bioimpedance and D dilution also improved in group A, P < 0.05, whereas weight increased in group B. Conclusions. Increasing the diffusive component of sodium removal whilst maintaining ultrafiltration is associated with improvements in BP, thirst and fluid status. The lack of effect seen with uncompensated low-sodium dialysate suggests that these benefits cannot be achieved by manipulation of dialysate sodium removal alone. These observations provide valuable information of the design of future randomized studies to establish the clinical role for low-sodium dialysis fluids.
50.	Devuyst, O, et al. (författare) Response to 'Aquaporin-1 and sodium transport in the peritoneal membrane - need for more research?' 2006 Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 70:9, s. 1663-1664 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)

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