| 1. |
- Axelsson, Josefin, et al.
(författare)
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Rapid, dynamic changes in glomerular permeability to macromolecules during systemic Angiotensin II (AngII) infusion in rats.
- 2012
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 303:6, s. 790-799
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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.
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| 2. |
- Axelsson, Josefin, et al.
(författare)
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Size-selectivity of a synthetic high-flux and a high cut-off dialyzing membrane compared to that of the rat glomerular filtration barrier
- 2012
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Ingår i: Journal of Membrane Science. - : Elsevier BV. - 0376-7388. ; 413, s. 29-37
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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.
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| 3. |
- Bakoush, Omran, et al.
(författare)
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Effect of diabetes mellitus on the recovery of changes in renal functions and glomerular permeability following reversible 24-hour unilateral ureteral obstruction
- 2018
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Ingår i: Journal of Diabetes. - : Wiley. - 1753-0393 .- 1753-0407.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Following reversal of short periods of ureteral obstruction (UO), glomerular and tubular renal dysfunction recovers with time. Diabetes mellitus (DM) affects glomerular function; thus, the ability of diabetic kidneys to recover from UO may be impaired. This study investigated the effects of long-term DM on the recovery of glomerular and tubular function, as well as permeability of the glomerular filtration barrier (GFB), after unilateral UO (UUO) reversal. Methods: Diabetes mellitus was induced in Wistar rats by intraperitoneal streptozotocin. All diabetic and age-matched control rats underwent reversible 24-hour left UUO. The renal function of both kidneys was measured using clearance techniques 3 hours and 7 and 30 days after UUO reversal. Glomerular permeability was assessed by measuring the glomerular sieving coefficients for fluorescein isothiocyanate-conjugated Ficoll (molecular radius: 20-90 Å). Results: Unilateral UO induced transient changes in the size selectivity of GFB small pores. However, the size selectivity function of large pores had not returned to baseline even 30 days after UUO reversal. Diabetes mellitus caused exaggerated early alterations in glomerular hemodynamic and tubular function, as well as size selectivity dysfunction of both small and large pores. At 30 days after UUO reversal, despite glomerular hemodynamic and tubular function and the size selectivity of small pores returning to normal in both diabetic and non-diabetic rats, the residual size selectivity dysfunction of large pores was more severe in diabetic rats. Conclusion: Unilateral UO caused long-term dysfunction in the size selectivity of large pores of the GFB. In addition, DM significantly exaggerated this dysfunction, indicating a more ominous outcome in diabetic kidneys following UUO.
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| 4. |
- Bark, Björn, et al.
(författare)
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Plasma Volume Expansion by 0.9% NaCl During sepsis/SIRS, After Hemorrhage, and During a Normal State.
- 2013
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Ingår i: Shock. - 1540-0514. ; 40:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the degree of plasma volume expansion by 0.9% NaCl in relation to the infused volume, in sepsis/SIRS (systemic inflammatory response syndrome), after a standardized hemorrhage, and in a normal condition. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: Thirty anesthetized adult male rats. INTERVENTIONS: The study was performed in 3 groups: a sepsis/SIRS group (the S group), in which sepsis/SIRS was induced by cecal ligation and incision, a hemorrhage group (the H group), in which the rats were left without intervention for 4 hrs, and bled 8 mL/kg thereafter. The study also included a group that was left without intervention (the N group). Then, 4 hrs after baseline, all 3 groups were given an infusion of 0.9% NaCl (32 mL/kg) for 15 mins. Baseline was defined as the time point when the surgical preparation was finished. MEASUREMENTS AND MAIN RESULTS: Plasma volumes were measured using I-albumin dilution technique at baseline, after 4 hrs, and 20 mins after the end of infusion. The plasma volume-expanding effect 20 mins after end of infusion was 0.6 ± 2.9% in the S group, 20 ± 6.4% in the H group and 12 ± 11% in the N group, compared to just before start of infusion. CONCLUSIONS: The present study in rats showed that the plasma volume-expanding effect after an infusion of 0.9% NaCl was smaller in a septic/SIRS state than after hemorrhage and in a normal state. This indicates that the plasma volume expanding effect of a crystalloid in sepsis/SIRS is dependent on pathophysiological changes.
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| 5. |
- Bimpisidis, Zisis, et al.
(författare)
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Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease
- 2017
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 292, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease.
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| 6. |
- Blomberg, Frida, et al.
(författare)
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Swedish and English word ratings of imageability, familiarity and age of acquisition are highly correlated
- 2015
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Ingår i: Nordic Journal of Linguistics. - 0332-5865 .- 1502-4717. ; 38:3, s. 351-364
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Tidskriftsartikel (refereegranskat)abstract
- At present, there is no comprehensive psycholinguistic database containing Swedish words with ratings of word properties such as e.g. imageability, although researchers carrying out psycholinguistic studies in Swedish face the need to be able to control for and systematically vary such properties. The present study addressed this issue by investigating the possibility of transferring English word ratings to Swedish. Imageability, familiarity and age of acquisition (AoA) ratings were obtained for a sample of Swedish words (N = 99). These ratings were then compared with the corresponding English ratings from the Medical Research Council (MRC) Psycholinguistic Database (Coltheart 1981) using Spearman correlation. Swedish and English word ratings were found to be highly correlated for imageability and AoA, and moderately correlated for familiarity. Following these results, we suggest that, in general, ratings of these variables can be reliably transferred between the two languages, although some caution should be taken, since for some individual words, some ratings might differ substantially for their Swedish and English translations.
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| 7. |
- Carlborg, Carl Fredrik, 1981-, et al.
(författare)
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BEYOND PDMS: : OFF-STOCHIOMETRY THIOL-ENE BASED SOFT LITHOGRAPHY FOR RAPID PROTOTYPING OF MICROFLUIDIC DEVICES
- 2010
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Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (micro TAS 2010). - 9781618390622 ; , s. 70-72
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Konferensbidrag (refereegranskat)abstract
- We present an easy to use, rapid fabrication platform for microfluidic systems, based on micro-molding of novel thiolene based polymer formulations. The novel fabrication platform addresses major drawbacks of PDMS by allowing large freedom in material and surface properties, including: (photo)patterning of stable surface modifications, bonding without plasma treatment, rapid UV or thermal curing, variable E-modulus, minimized leaching of uncured components [1] and suppressed non-specific binding of biomolecules [2]. This process is potentially suited for both rapid prototyping in the laboratory and medium-scale commercial production, bridging the “development gap”.
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| 8. |
- Carlborg, Carl Fredrik, et al.
(författare)
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Beyond PDMS: off-stoichiometry thiol–ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices
- 2011
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Ingår i: Lab on a Chip. - : RSC Publishing. - 1473-0197 .- 1473-0189. ; 11:18, s. 3136-3147
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Tidskriftsartikel (refereegranskat)abstract
- In this article we introduce a novel polymer platform based on off-stoichiometry thiol–enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol–ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials.
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| 9. |
- Dolinina, Julia, et al.
(författare)
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Glomerular hyperpermeability after acute unilateral ureteral obstruction : Effects of Tempol, NOS, RhoA, and Rac-1 inhibition
- 2018
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 315:3, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120-or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean θ for Ficoll70Å was increased (P < 0.01) from 2.2 ± 0.5 × 10−5 (baseline) to 10.6 ± 10 × 10−5 15 min postrelease (highest value). After 180-min UUO, mean θ for Ficoll70Å was further increased (P < 0.001) from 1.4 ± 0.5 × 10−5 (baseline) to 40 ± 10 × 10−5 at 5 min postrelease (highest value). Administration of a reactive oxygen species (ROS) scavenger (Tempol; 1 mg·kg−1·min−1) partly abrogated the permeability effects following 120-min UUO but not after 180 min. Moreover, administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or Rac-1 inhibition did not ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the first time, that acute UUO results in marked elevations in glomerular permeability. In addition, our data suggest a time-dependent pathophysiology of UUO-induced hyperpermeability, where reactive oxygen species generation may play an important role in the early stages.
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| 10. |
- Dolinina, Julia, et al.
(författare)
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Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species
- 2016
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 311:5, s. 984-990
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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.
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