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Sökning: WFRF:(Öberg Carl)

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1.
  • Wallman, Carl-Gustaf, et al. (författare)
  • Tema Vintermodell : etapp 2, huvudrapport
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Syftet med Vintermodellen är att beräkna och värdera de väsentligaste konsekvenserna för trafikanter, väghållare och samhälle av olika strategier och åtgärder inom vinterväghållningen. Huvudrapporten är i sig en sammanfattning av de rapporter som beskriver Vintermodellens olika delmodeller. Navet i Vintermodellen är Väglagsmodellen, som utgående från väderdata, vidtagna väghållningsåtgärder och trafik beräknar väglaget timme för timme under vintersäsongen. Väglagsmodellen styr beräkningarna i de olika effektmodellerna: Olycksmodellen, Framkomlighetsmodellen, Fordonskostnadsmodellen, Miljömodellen och Modellen för väghållarkostnader. I Olycksmodellen beräknas olyckskvoter, olyckstyper och konsekvenser, allt kopplat till olika väglag och deras varaktigheter.I Framkomlighetsmodellen beräknas olika väglags effekt på medelhastigheter och restider.I Fordonskostnadsmodellen beräknas kostnader för bränsleförbrukning och korrosion på grund av vägsalt.I Miljömodellen beräknas konsekvenserna för vägnära vegetation av vägsalt.I Modellen för väghållarkostnader beräknas dels direkta kostnader för åtgärderna, dels kostnader för skador och slitage på beläggning, vägmarkeringar etc. som följd av vinterväghållningsåtgärder.
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5.
  • 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.
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6.
  • 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.
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7.
  • Bakoush, Omran, et al. (författare)
  • Effect of diabetes mellitus on the recovery of changes in renal functions and glomerular permeability following reversible 24-hour unilateral ureteral obstruction
  • 2018
  • Ingår i: Journal of Diabetes. - : Wiley. - 1753-0393 .- 1753-0407.
  • 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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8.
  • Bark, Björn, et al. (författare)
  • Plasma Volume Expansion by 0.9% NaCl During sepsis/SIRS, After Hemorrhage, and During a Normal State.
  • 2013
  • Ingår i: Shock. - 1540-0514. ; 40:1, s. 59-64
  • 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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9.
  • Bergling, Karin, et al. (författare)
  • Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR) : A randomised controlled crossover trial
  • 2022
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 42:6, s. 615-621
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The continuous global rise of end-stage kidney disease creates a growing demand of economically beneficial home-based kidney replacement therapies such as peritoneal dialysis (PD). However, undesirable absorption and exposure of peritoneal tissues to glucose remain major limitations of PD. Methods: We compared a reference (standard) automated PD regimen 6 × 2 L 1.36% glucose (76 mmol/L) over 9 h with a novel, theoretically glucose sparing (optimised) prescription consisting of ‘ultrafiltration cycles’ with high glucose strength (126 mmol/L) and ‘clearance cycles’ with ultra-low, physiological glucose (5 mmol/L) for approximately 40% of the treatment time. Twenty-one prevalent PD patients underwent the optimised regimen (7 × 2 L 2.27% glucose + 5 × 2 L 0.1% glucose over 8 h) and the standard regimen in a crossover fashion. Six patients were excluded from data analysis. Results: Median glucose absorption was 43 g (IQR 41–54) and 44 g (40–55) for the standard and optimised intervention, respectively (p = 1). Ultrafiltration volume, weekly Kt/V creatinine and urea were significantly improved during optimised interventions, while no difference in sodium removal was detected. Post hoc analysis showed significantly improved ultrafiltration efficiency (ml ultrafiltration per gram absorbed glucose) during optimised regimens. No adverse events were observed except one incidence of drain pain. Conclusion: Optimised treatments were feasible and well tolerated in this small pilot study. Despite no difference in absorbed glucose, results indicate possible improvements of ultrafiltration efficiency and small solute clearances by optimised regimens. Use of optimised prescriptions as glucose sparing strategy should be evaluated in larger study populations.
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10.
  • Bergling, Karin, et al. (författare)
  • Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR) : Study protocol for a randomized controlled crossover trial
  • 2020
  • Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having "UF cycles"using a higher glucose concentration, and "Clearance cycles"using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. Methods: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 and 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either standard APD (6 × 2 L 1.36% over 9 h) or optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 h). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment, and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the optimized and standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea, and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. Discussion: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies. Trial registration: ClinicalTrials.gov identifier: NCT04017572. Registration date: July 12, 2019, retrospectively registered.
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11.
  • Bergling, Karin, et al. (författare)
  • Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats
  • 2022
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 33:10, s. 1857-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis. We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during peritoneal dialysis in rats. However, more recently we found that phlorizin, a dual blocker of sodium glucose co-transporter 1 and 2, reduces glucose diffusion in peritoneal dialysis. Therefore, either inhibiting sodium glucose co-transporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in peritoneal dialysis. Methods: We tested a selective blocker of sodium glucose co-transporter 1, mizagliflozin, as well as phloretin, a non-selective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of peritoneal dialysis. Results: Intraperitoneal phloretin treatment reduced glucose absorption by more than 30% and resulted in a more than 50% higher ultrafiltration rate compared to control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per mmol sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport. Conclusions: Taken together, our present and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in peritoneal dialysis.
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12.
  • Bimpisidis, Zisis, et al. (författare)
  • 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
  • Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 292, s. 113-124
  • 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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13.
  • Blomberg, Frida, et al. (författare)
  • Swedish and English word ratings of imageability, familiarity and age of acquisition are highly correlated
  • 2015
  • Ingår i: Nordic Journal of Linguistics. - 0332-5865 .- 1502-4717. ; 38:3, s. 351-364
  • 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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14.
  • Caporale, N., et al. (författare)
  • From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
  • Tidskriftsartikel (refereegranskat)abstract
    • Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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15.
  • Carlborg, Carl Fredrik, 1981-, et al. (författare)
  • BEYOND PDMS: : OFF-STOCHIOMETRY THIOL-ENE BASED SOFT LITHOGRAPHY FOR RAPID PROTOTYPING OF MICROFLUIDIC DEVICES
  • 2010
  • Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (micro TAS 2010). - 9781618390622 ; , s. 70-72
  • 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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16.
  • Carlborg, Carl Fredrik, et al. (författare)
  • Beyond PDMS: off-stoichiometry thiol–ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices
  • 2011
  • Ingår i: Lab on a Chip. - : RSC Publishing. - 1473-0197 .- 1473-0189. ; 11:18, s. 3136-3147
  • 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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17.
  • Cederqvist, Lars, et al. (författare)
  • Improved process stability during friction stir welding of 5 cm thick copper canisters through shoulder geometry and parameter studies
  • 2009
  • Ingår i: Science and technology of welding and joining. - London : Institute of Materials. - 1362-1718 .- 1743-2936. ; 14:2, s. 178-184
  • Tidskriftsartikel (refereegranskat)abstract
    • The spent nuclear fuel from Swedish power plants will be placed in copper canisters that are sealed with friction stir welding and the stability and robustness of this process is now being optimised in three steps: first, the shoulder geometry was identified that produced the most stable weld cycle, then the welding parameters were optimised for that geometry with regards to stability, and finally, the chosen geometry and welding parameters were verified and evaluated during multiple weld cycles. The shoulder study showed that stable welds could be produced repeatedly with a convex scroll geometry which proved more stable than various concave and flat scroll geometries. In the subsequent parameter study, not only were the most stable values for the welding parameters derived, but a clear relationship was shown between power input and tool temperature. This relationship can be used to more accurately control the process within the parameter windows, not only for this application but for other applications where the welding temperature needs to be kept within a specified range. Similarly, the potential of the convex scroll shoulder geometry for use in applications with other metals and thicknesses is evident.
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18.
  • Chaudhry, A, et al. (författare)
  • Expression of transforming growth factor b1, b2, b3 in neuroendocrine tumors of the digestive system
  • 1994
  • Ingår i: Anticancer Res. ; 14, s. 2085-
  • Tidskriftsartikel (refereegranskat)abstract
    • Ligand induced activation of the beta-receptor for platelet-derived growth factor (PDGF) leads to activation of Src family tyrosine kinases. We have explored the possibility that the receptor itself is a substrate for Src. We show that Tyr934 in the kinase domain of the PDGF receptor is phosphorylated by Src. Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced with a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB. In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization. Whereas the motility responses of cells expressing wild-type beta-receptors were attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced. In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of protein kinase C, whereas the chemotaxis of cells expressing the wild-type beta-receptor was less affected. Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells. In conclusion, the characteristics of the Y934F mutant suggest that the phosphorylation of Tyr934 by Src negatively modulates a signal transduction pathway leading to motility responses which involves phospholipase C-gamma, and shifts the response to increased mitogenicity.
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19.
  • Cheng, Peifu, et al. (författare)
  • High-Performance Hemofiltration via Molecular Sieving and Ultra-Low Friction in Carbon Nanotube Capillary Membranes
  • 2023
  • Ingår i: Advanced Functional Materials. - 1616-301X. ; 33:50
  • Tidskriftsartikel (refereegranskat)abstract
    • Conventional dialyzer membranes typically comprise of unevenly distributed polydisperse, tortuous, rough pores, embedded in relatively thick ≈20–50 µm polymer layers wherein separation occurs via size exclusion as well as differences in diffusivity of the permeating species. However, transport in such polymeric pores is increasingly hindered as the molecule size approaches the pore dimension, resulting in significant retention of undesirable middle molecules (≥15–60 kDa) and uremic toxins. Enhanced removal of middle molecules is usually accompanied by high albumin loss (≈66 kDa) causing hypoalbuminemia. Here, the scalable bottom-up fabrication of wafer-scale carbon nanotube (CNT) membranes with highly aligned, low-friction, straight-channels/capillaries and narrow pore-diameter distributions (≈0.5–4.5 nm) is demonstrated, to overcome persistent challenges in hemofiltration/hemodialysis. Using fluorescein isothiocyanate (FITC)-Ficoll 70 and albumin in phosphate buffered saline (PBS) as well as in bovine blood plasma, it is shown that CNT membranes can allow for significantly higher hydraulic permeability (more than an order of magnitude when normalized to pore area) than commercial high-flux hemofiltration/hemodialysis membranes (HF 400), as well as greatly enhance removal of middle molecules while maintaining comparable albumin retention. These findings are rationalized via an N-pore transport model that highlights the critical role of molecular flexing and deformation during size-selective transport within nanoscale confinements of the CNTs. The unique transport characteristics of CNTs coupled with size-exclusion and wafer-scale fabrication offer transformative advances for hemofiltration, and the obtained insight into molecular transport can aid advancements in several other bio-systems/applications beyond hemofiltration/hemodialysis.
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20.
  • Dolinina, Julia, et al. (författare)
  • Clemizole and La3+ salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo
  • 2021
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca2+ influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La3+ salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability. Anesthetized male Sprague-Dawley rats were infused with Ang II (80 ng kg–1min–1) alone, or together with clemizole or low-dose La3+ (activates TRPC5, blocks TRPC6) or high-dose La3+ (blocks both TRPC5 and TRPC6). Plasma and urine samples were taken during baseline and at 5 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients for Ficoll 10–80 Å (1–8 nm). Ang II infusion evoked glomerular hyperpermeability to large Ficolls (50–80 Å), which was ameliorated by clemizole, having no significant effect on glomerular filtration rate (GFR) or Ang II-mediated increase in mean arterial pressure (ΔMAP). In contrast, high- and low-dose La3+ significantly lowered ΔMAP and reduced Ang II-induced hyperpermeability. Combined, clemizole and low-dose La3+ were less effective at ameliorating Ang II-induced glomerular hyperpermeability than low-dose La3+ alone. In conclusion, our data show that both clemizole and La3+ are effective against Ang II-induced glomerular hyperpermeability, with differential effects on blood pressure. Further research using more specific blockers of TRPC5 and TRPC6 should be performed to reveal the underlying mechanisms.
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21.
  • Dolinina, Julia, et al. (författare)
  • Glomerular hyperpermeability after acute unilateral ureteral obstruction : Effects of Tempol, NOS, RhoA, and Rac-1 inhibition
  • 2018
  • Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 315:3, s. 445-453
  • 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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22.
  • 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.
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23.
  • Dolinina, Julia, et al. (författare)
  • Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETa receptor
  • 2019
  • Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 316:6, s. 1173-1179
  • Tidskriftsartikel (refereegranskat)abstract
    • Dolinina J, Rippe A, Öberg CM. Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETA receptor. Am J Physiol Renal Physiol 316: F1173–F1179, 2019. First published March 13, 2019; doi:10.1152/ajprenal.00040.2019.—Emerging evidence indicates that endogenous production of endothelin (ET)-1, a 21-amino acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are, however, currently not known. Here, we used size-exclusion chromatography to measure glomerular sieving coefficients for neutral FITC-Ficoll (molecular Stokes-Einstein radius: 15–80 Å, molecular weight: 70 kDa/400 kDa) in anesthetized male Sprague-Dawley rats (n = 12) at baseline and at 5, 15, 30, and 60 min after intravenous administration of ET-1. In separate experiments, ET-1 was given together with the selective ET type A (ETA) or ET type B (ETB) receptor antagonists JKC-301 and BQ-788, respectively. At both 15 and 30 min postadministration, the glomerular sieving coefficient for macromolecular Ficoll (70 Å) was significantly increased to 4.4 x 10-5  0.7 x 10-5 (P = 0.024) and 4.5 x 10-5  0.8 x 10-5 (P = 0.007), respectively, compared with baseline (2.2 x 10-5  0.4 x10-5). Decreased urine production after ET-1 prevented the use of higher doses of ET-1. Data analysis using the two-pore model indicated changes in large-pore permeability after ET-1, with no changes in the small-pore pathway. Administration of ETA blocker abrogated the permeability changes induced by ET-1 at 30 min, whereas blockade of ETB receptors was ineffective. Mean arterial pressure was only significantly increased at 60 min, being 123  4 mmHg compared with 111  2 mmHg at baseline (P = 0.02). We conclude that ET-1 evoked small, delayed, and sustained increases in glomerular permeability, mediated via the ETA receptor.
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24.
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25.
  • Eriksson, Carl, 1981-, et al. (författare)
  • Real-world effectiveness of vedolizumab in inflammatory bowel disease : week 52 results from the Swedish prospective multicentre SVEAH study
  • 2021
  • Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.
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26.
  • Everitt, Carl-Magnus, 1988-, et al. (författare)
  • An imprint method to produce surface asperities for EHL and RCF experiments
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • A method was developed for creating single well defined surface asperities using an imprint technique. The proposed method can be used to create asperities of different heights and widths in the micrometre range. The technique for creating single surface asperities is based on rolling a hard disc with indents against a soft disc. The contact pressure will cause plastic deformation forcing material into the indents to create the asperities. The height of the asperities can be controlled by adjusting the applied force. After initial reshaping during the run-in process, the asperities were strong enough to survive more than 35 million EHL contact cycles. The method should thus be of great interest for the researchers investigating rolling contact fatigue experimentally. The method could also aid the research of the run in process by enabling tracing the development of specific surface defects. Since the method can produce high and strong asperities it might also prove useful for investigations of exactly how asperities deform under sever contacts conditions.  
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27.
  • Everitt, Carl-Magnus, 1988-, et al. (författare)
  • An imprint method to produce surface asperities for EHL and RCF experiments
  • 2021
  • Ingår i: MethodsX. - : Elsevier BV. - 1258-780X .- 2215-0161. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • A method was developed for creating single well-defined surface asperities using an imprint technique. The proposed method enables: • Creation of well-defined micrometre high asperities • Creation of asperities which survived more than 35 million EHL contact cycles • Damage tracing thanks to the possibility to control the damage initiation sites.The technique is based on rolling a hard disc with indents against a soft disc for creating single surface asperities. The contact pressure causes plastic deformation forcing material into the indents to create the asperities. The height of the asperities can be controlled by adjusting the applied force. After initial reshaping during the run-in process, the asperities were strong enough to survive more than 35 million elastohydrodynamic lubrication cycles, which should be of great interest for the researchers who investigate rolling contact fatigue experimentally. The method could also aid the research on the run-in process by enabling tracing the development of specific surface defects. Since the method can produce high and strong asperities it might also prove useful for investigations how asperities deform under sever contact conditions.
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28.
  • Fruhwürth, Stefanie, 1987, et al. (författare)
  • TREM2 is down-regulated by HSV1 in microglia and involved in antiviral defense in the brain
  • 2023
  • Ingår i: Science Advances. - 2375-2548. ; 9:33
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunological control of viral infections in the brain exerts immediate protection and also long-term maintenance of brain integrity. Microglia are important for antiviral defense in the brain. Here, we report that herpes simplex virus type 1 (HSV1) infection of human induced pluripotent stem cell (hiPSC)-derived microglia down-regulates expression of genes in the TREM2 pathway. TREM2 was found to be important for virus-induced IFNB induction through the DNA-sensing cGAS-STING pathway in microglia and for phagocytosis of HSV1-infected neurons. Consequently, TREM2 depletion increased susceptibility to HSV1 infection in human microglia-neuron cocultures and in the mouse brain. TREM2 augmented STING signaling and activation of downstream targets TBK1 and IRF3. Thus, TREM2 is important for the antiviral immune response in microglia. Since TREM2 loss-of-function mutations and HSV1 serological status are both linked to Alzheimer's disease, this work poses the question whether genetic or virus-induced alterations of TREM2 activity predispose to post-infection neurological pathologies.
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29.
  • Gennings, Chris, et al. (författare)
  • Incorporating regulatory guideline values in analysis of epidemiology data
  • 2018
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 120, s. 535-543
  • Tidskriftsartikel (refereegranskat)abstract
    • Fundamental to regulatory guidelines is to identify chemicals that are implicated with adverse human health effects and inform public health risk assessors about “acceptable ranges” of such environmental exposures (e.g., from consumer products and pesticides). The process is made more difficult when accounting for complex human exposures to multiple environmental chemicals. Herein we propose a new class of nonlinear statistical models for human data that incorporate and evaluate regulatory guideline values into analyses of health effects of exposure to chemical mixtures using so-called ‘desirability functions’ (DFs). The DFs are incorporated into nonlinear regression models to allow for the simultaneous estimation of points of departure for risk assessment of combinations of individual substances that are parts of chemical mixtures detected in humans. These are, in contrast to published so-called biomonitoring equivalent (BE) values and human biomonitoring (HBM) values that link regulatory guideline values from in vivo studies of single chemicals to internal concentrations monitored in humans. We illustrate the strategy through the analysis of prenatal concentrations of mixtures of 11 chemicals with suspected endocrine disrupting properties and two health effects: birth weight and language delay at 2.5 years. The strategy allows for the creation of a Mixture Desirability Function i.e., MDF, which is a uni-dimensional construct of the set of single chemical DFs; thus, it focuses the resulting inference to a single dimension for a more powerful one degree-of-freedom test of significance. Based on the application of this new method we conclude that the guideline values need to be lower than those for single chemicals when the chemicals are observed in combination to achieve a similar level of protection as was aimed for the individual chemicals. The proposed modeling may thus suggest data-driven uncertainty factors for single chemical risk assessment that takes environmental mixtures into account.
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30.
  • Gustafsson, Mats, et al. (författare)
  • Effekter av vinterdäck : en kunskapsöversikt
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Choice of winter tyres has, from mainly being a matter of safety and economic costs for wearing of road pavements, during later years also become a matter of inhalable particles formed during pavement wear from studded tyres and their negative effects on public health. Further, the tyres' effects on environment and noise have been illustrated in several studies. The issue is also complicated by the fact that tyre choice effects on traffic safety have several components, including such diverging parameters as friction and behaviour. Finally all aspects have to be evaluated from a socioeconomic point of view for society to be able to decide which kind of distribution of tyre types that is the most profitable. This report is a summary of current knowledge in this complex research field.
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31.
  • Helman, Jakob, et al. (författare)
  • High versus low ultrafiltration rates during experimental peritoneal dialysis in rats : Acute effects on plasma volume and systemic haemodynamics
  • 2023
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 43:1, s. 84-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates. Methods: Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate (N = 7) induced by 8.5% glucose and a low UF group (N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment. Results: No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of −7 mL (−10.7% (95% confidence interval: −13.8% to −7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL). Conclusion: Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.
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32.
  • Hobro, Sture, et al. (författare)
  • Dialysis as a Novel Adjuvant Treatment for Malignant Cancers
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:20
  • Forskningsöversikt (refereegranskat)abstract
    • Cancer metabolism is characterized by an increased utilization of fermentable fuels, such as glucose and glutamine, which support cancer cell survival by increasing resistance to both oxidative stress and the inherent immune system in humans. Dialysis has the power to shift the patient from a state dependent on glucose and glutamine to a ketogenic condition (KC) combined with low glutamine levels—thereby forcing ATP production through the Krebs cycle. By the force of dialysis, the cancer cells will be deprived of their preferred fermentable fuels, disrupting major metabolic pathways important for the ability of the cancer cells to survive. Dialysis has the potential to reduce glucose levels below physiological levels, concurrently increase blood ketone body levels and reduce glutamine levels, which may further reinforce the impact of the KC. Importantly, ketones also induce epigenetic changes imposed by histone deacetylates (HDAC) activity (Class I and Class IIa) known to play an important role in cancer metabolism. Thus, dialysis could be an impactful and safe adjuvant treatment, sensitizing cancer cells to traditional cancer treatments (TCTs), potentially making these significantly more efficient.
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33.
  • Karsten, Agneta Linder-Aronson, et al. (författare)
  • The resistance to axial dislodgement of nickel titanium compression arch wire hooks - an in vitro study
  • 2019
  • Ingår i: Australasian Orthodontic Journal. - : Australian Society of Orthodontists. - 2207-7472. ; 35:1, s. 21-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the level of force required to axially dislodge nickel titanium compression hooks (Trillium Compression Hook (TM), Hespeler Orthodontics) placed on orthodontic arch wires in vitro. Materials and methods: Nickel titanium compression hooks were placed on arch wires with a specially designed pair of pliers. The resistance to axial dislodgement was tested on a total of 260 hooks placed in a standardised way on round (0.016 '', 0.018 '', 0.020 ''), square (0.020 x 0.020 '') and rectangular (0.016 x 0.022 '', 0.019 x 0.025 '', 0.021 x 0.025 '') stainless steel (Rocky Mountain Orthodontics), nickel titanium, or beta-titanium (Hespeler Orthodontics) arch wires. The forces required to displace the hooks were recorded using an Instron tensile testing machine. The data were compared with the results reported in similar studies on stainless steel crimpable arch wire hooks. Results: The forces required to dislodge the compression hooks varied between 45.0 N and 161.9 N. The hook's resistance to dislodgement was found to be high in all tested hook/wire combinations. The lowest recorded average dislodging force was found in the 0.020 '' nickel titanium group and the highest average force was in the 0.016 x 0.022 '' beta-titanium group. Conclusion: The forces needed to dislodge the tested nickel titanium compression arch wire hooks exceed the force levels previously reported for stainless steel crimpable arch wire hooks.
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34.
  • Ledberg, Sofia Knöchel, 1972- (författare)
  • Governing the Military : Professional Autonomy in the Chinese People's Liberation Army
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The reform process that has been underway in China the past 30 years has affected most parts of Chinese society. In regard to core branches of the civilian state administration, public administration research provides evidence of far-reaching decentralization, marketization, and a relaxation of direct political control within many policy areas. Despite the fact that the military in any Marxist-Leninist state is an indispensable part of the state administration, it is rarely included in research on the Chinese state administrations. In this dissertation, it is argued that the military is intrinsically linked to the overall political stability of the Chinese state not only because it constitutes one of the most central branches of the Chinese cadre administration, but also given its close connection to the ruling communist party. Hence it deserves greater research focus.The overarching focus of this study is political control and governance vis-à-vis the Chinese military. Contrary to previous studies that have approached the issue of control by investigating military infringement on civilian policy making, the analysis here illustrates that the structures and the underlying logic of control are better captured by a study of the professional autonomy of the Chinese military officer corps. Professional autonomy is investigated within the military education system, given that education is a central undertaking for any profession.By suggesting a new approach to the study of the relationship between the political entities of the state and the military, an approach which makes use of insights from both the political science subfield of public administration and the sociology of professions, this dissertation makes important theoretical and analytical contributions to the field of civil-military relations. Yet the usefulness of the actor-centered approach put forward here, which focuses on the autonomy of the profession within the organization, reaches beyond the immediate study of the military and can be used in any analysis of power relations between the political entities of the state and its administrations. This dissertation also contributes to increase the understanding of Chinese military education, which is one of the military’s most important peace time undertakings.
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35.
  • Lubbad, Loay, et al. (författare)
  • Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.
  • 2015
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20-90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50-69 Å = 0.001 vs. 0.0002, and θ for 70-90 Å = 0.0007 vs. 0.00006, P < 0.001), while θ for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (θ for 36-49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes.
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36.
  • Malmgren, Linnea, et al. (författare)
  • The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
  • 2023
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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37.
  • Martus, Giedre, et al. (författare)
  • Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis
  • 2023
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 43:2, s. 145-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. Methods: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. Results: Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p < 0.05) being 196 µL/min (IQR 178–213) for phlorizin-treated animals compared to 238 µL/min (IQR 233–268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D0) was significantly higher (p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63–0.67) compared to 0.61 (IQR 0.60–0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. Conclusion: Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.
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38.
  • Martus, Giedre, et al. (författare)
  • Novel Method for Osmotic Conductance to Glucose in Peritoneal Dialysis
  • 2020
  • Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 5:11, s. 1974-1981
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The osmotic conductance to glucose (OCG) is a crucial determinant of ultrafiltration (UF) in peritoneal dialysis (PD) patients and can be used to monitor membrane integrity in patients on long-term PD. It has been proposed that OCG can be assessed based on drained volumes in 2 consecutive 1-hour glucose dwells, usually 1.5% and 4.25% glucose, in a so-called double mini-peritoneal equilibration test (dm-PET). However, recent data indicated that the dm-PET provides a poor estimate of OCG unless the residual volume (RV) is taken into account. We introduce an easy, robust, and accurate method to measure OCG and compare it with conventional methods. Methods: In a prospective cohort of 21 PD patients, a modified version of the dm-PET was performed, along with the determination of RV before, between, and after dwells. Based on computer simulations derived from the 3-pore model (TPM) for membrane permeability, we developed and validated a novel single-dwell method to estimate OCG. We next validated the equation in an independent cohort consisting of 32 PD patients. Results: Single-dwell OCG correlated more closely with actual UF (r = 0.94 vs. r = 0.07 for conventional dm-PET), sodium sieving, and free water transport (FWT) compared with other methods. These findings were replicated in the validation cohort in which OCG calculated using the single-dwell method closely correlated with parameters of osmotic water transport, even when RV was not taken into account, using only drained volumes. Conclusion: We propose a novel, easy, and robust single-dwell method to determine OCG in individual patients and to monitor membrane integrity over time on PD.
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39.
  • Martus, Giedre, et al. (författare)
  • SGLT2 inhibition does not reduce glucose absorption during experimental peritoneal dialysis
  • 2021
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 41:4, s. 373-380
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. Methods: We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. Results: SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145–178) in sham animals and 157 mg 95% CI (137–172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425–494) and 472 mg 95% CI (420–506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. Conclusion: We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.
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40.
  • Morelle, Johann, et al. (författare)
  • ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults : Classification, measurement, interpretation and rationale for intervention
  • 2021
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 41:4, s. 352-372
  • Tidskriftsartikel (refereegranskat)abstract
    • Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1. Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point) Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point) Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point) Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B) Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point) Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and ‘lymphatic’ reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point) Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point)
  •  
41.
  • Morelle, Johann, et al. (författare)
  • Рекомендации международного общества перитонеального диализа по оценке дисфункции перитонеальной мембраны у взрослых : классификация, методы оценки, интерпретация и обоснования для вмешательства
  • 2023
  • Ingår i: Nephrology and Dialysis. - 1680-4422. ; 25:2, s. 232-266
  • Forskningsöversikt (refereegranskat)abstract
    • Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1.
  •  
42.
  • NILSSON, JAN, et al. (författare)
  • Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology
  • 2016
  • Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 58:1-2, s. 40-50
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS.MATERIALS AND METHODS: The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model.RESULTS: In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively.CONCLUSION: This study shows that it is possible to manage DRS measurements through the liver capsule and that surface DRS measurements are representative of the whole liver. The results are consistent with data published earlier on the combination of liver chromophores. The results encourage us to proceed with in vivo measurements for further quantification of the liver's composition and assessment of parenchymal damage such as steatosis and fibrosis grade.
  •  
43.
  •  
44.
  • Rippe, Bengt, et al. (författare)
  • Albumin Turnover in Peritoneal and Hemodialysis
  • 2016
  • Ingår i: Seminars in Dialysis. - : Wiley. - 0894-0959. ; 29:6, s. 458-462
  • Tidskriftsartikel (refereegranskat)abstract
    • The turnover of albumin is increased in both peritoneal dialysis (PD) and hemodialysis (HD) due to increased external losses, normally leading to compensatory increases in the hepatic albumin synthesis. The normal rate of albumin synthesis is on the order of 12 g/day corresponding to an equally large albumin fractional catabolic rate of ~4% daily. Most albumin catabolism is assumed to occur in the endothelium, but there is also renal and hepatic catabolism and leakage into the gastrointestinal tract. In PD the daily losses are on the order of 5 g/day. There are also external albumin losses in HD, particularly when high-performance membranes are used, the losses per session ranging between 1 and 8 g (or more). The dialytic albumin losses cannot be detected by assessing the transcapillary escape rate of albumin from the plasma compartment to the interstitium. In PD, tracer albumin that has been injected into the peritoneal fluid is absorbed to the tissues surrounding the peritoneal cavity without much edema formation, due to the process of "volume recirculation". A small fraction of the dialysate albumin tracer (0.2-0.3 ml/minute) is directly reabsorbed to the plasma via the lymphatics. A significant portion of dialysis patients are affected by chronic inflammation, such as in the malnutrition inflammation and atherosclerosis syndrome, which is also associated with cardiovascular mortality and fluid overload. These patients usually have a reduced ability to compensate for external losses of albumin, which may result in hypoalbuminemia. Reduced plasma albumin levels in dialysis patients may thus be regarded as a sign of chronic inflammation rather than reflecting malnutrition.
  •  
45.
  • Rippe, Bengt, et al. (författare)
  • Counterpoint: Defending Pore Theory.
  • 2015
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 1718-4304. ; 35:1, s. 9-13
  • Tidskriftsartikel (refereegranskat)
  •  
46.
  • Rippe, Bengt, et al. (författare)
  • IS ADAPTED APD THEORETICALLY MORE EFFICIENT THAN CONVENTIONAL APD?
  • 2016
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 1718-4304.
  • Tidskriftsartikel (refereegranskat)abstract
    • ♦ Background: A modified version of automated peritoneal dialysis (APD) using not only variable dwell times but also variable fill volumes has been tested against conventional APD (cAPD) with fixed dwell volumes in a randomized controlled clinical study. The results have indicated that the modified schedule for APD, denoted adapted APD (aAPD), can lead to improved small solute clearances, and, above all, a markedly increased sodium removal (NaR). To theoretically test these results, we have modeled aAPD vs cAPD in computer simulations using the 3-pore model (TPM). ♦ Methods: The TPM, modified by including a transient, initial inflation of small solute mass transfer area coefficients (PS values), was employed. For simulations of osmotic ultrafiltration (UF), the TPM uses a constantly inflated value for PS for glucose and also a reduced value for PS for Na+, setting the peritoneal lymphatic reabsorption term at 0.3 mL/min. The simulations were performed by assuming that increases in intraperitoneal hydrostatic pressure (IPP) are transmitted to the capillary level (via vein compression) and therefore do not significantly affect the Starling balance. Furthermore, the effective peritoneal surface area (A) was set to be variable as a function of intraperitoneal volume (IPV). ♦ Results: The simulations demonstrated a minor improvement of small solute clearances (~0.7 - 1.6%) and a very small improvement of UF and NaR in aAPD compared to cAPD. ♦ Conclusions: Due mainly to the increased fill volumes in 3 out of 5 dwells in aAPD, this modality caused minor increases in small solute clearances and marginal effects on UF and NaR. The computer simulations point to a need for accurate sodium determinations in aAPD, considering all the methodological problems and pitfalls relevant to determining dialysate Na+ concentrations and peritoneal sodium mass balance.
  •  
47.
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48.
  • Ruth, Jan-Erik, et al. (författare)
  • Old age and loneliness illustrated by the Zulliger
  • 1990
  • Ingår i: British Journal of Projective Psychology. - 0957-7785. ; 25:2, s. 61-73
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Investigated the personality structure in old age, focusing on sociability and loneliness, using the Zulliger Individual and Group Test among 32 noninstitutionalized elderly adults (aged 75–85 yrs) and 36 control adults (aged 31–60 yrs). 15 elderly Ss were considered to be sociable, and 17 were considered to be lonely. J. E. Exner's (1986) comprehensive Rorschach system was used to analyze the data. Sociable Ss were lively and independent, although slightly aggressive and hostile. They showed signs of helplessness and experienced feelings of uneasiness. These Ss retained more liveliness with respect to their basic personality structure compared with lonely Ss. Lonely Ss were more prone to withdraw and simplify their conception of the surrounding world.
  •  
49.
  • Sigurjonsson, Johann, et al. (författare)
  • A study of size-selective renal elimination using a novel human model
  • Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; , s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patientsundergoing Transcatheter Aortic Valve Implantation (TA VI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecularsize. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.
  •  
50.
  • Sivertsson, Ebba, et al. (författare)
  • Inhibition of mammalian target of rapamycin decreases intrarenal oxygen availability and alters glomerular permeability
  • 2018
  • Ingår i: American Journal of Physiology - Renal Physiology. - : AMER PHYSIOLOGICAL SOC. - 1931-857X .- 1522-1466. ; 314:5, s. F864-F872
  • Tidskriftsartikel (refereegranskat)abstract
    • An increased kidney oxygen consumption causing tissue hypoxia has been suggested to be a common pathway toward chronic kidney disease. The mammalian target of rapamycin (mTOR) regulates cell proliferation and mitochondrial function. mTOR inhibitors (e.g., rapamycin) are used clinically to prevent graft rejection. mTOR has been identified as a key player in diabetes, which has stimulated the use of mTOR inhibitors to counter diabetic nephropathy. However, the effect of mTOR inhibition on kidney oxygen consumption is unknown. Therefore, we investigated the effects of mTOR inhibition on in vivo kidney function, oxygen homeostasis, and glomerular permeability. Control and streptozotocin-induced diabetic rats were chronically treated with rapamycin, and the functional consequences were studied 14 days thereafter. In both groups, mTOR inhibition induced mitochondrial uncoupling, resulting in increased total kidney oxygen consumption and decreased intrarenal oxygen availability. Concomitantly, mTOR inhibition induced tubular injury, as estimated from urinary excretion of kidney injury molecule-1 (KIM-1) and reduced urinary protein excretion. The latter corresponded to reduced sieving coefficient for large molecules. In conclusion, mTOR inhibition induces mitochondrial dysfunction leading to decreased oxygen availability in normal and diabetic kidneys. which translates into increased KIM-1 in the urine. Reduced proteinuria after mTOR inhibition is an effect of reduced glomerular permeability for large molecules. Since hypoxia has been suggested as a common pathway in the development of chronic kidney disease, mTOR inhibition to patients with preexisting nephropathy should be used with caution, since it may accelerate the progression of the disease.
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