| 1. |
- Aanen, M C, et al.
(författare)
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A detailed analysis of sodium removal by peritoneal dialysis: comparison with predictions from the three-pore model of membrane function
- 2005
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 20:6, s. 1192-1200
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Tidskriftsartikel (refereegranskat)abstract
- Background. The development of fluid and salt retention is a potential problem for all peritoneal dialysis (PD) patients. Sodium removal by the peritoneum is predominantly determined by convective fluid loss but influenced by diffusion and sieving due to free water transport as predicted by the three-pore model (TPM). The aim of the study was to establish the effect of transport status, dwell length and glucose concentration on observed ultrafiltration (UF), dialysate sodium concentration ([Na+](D)) and removal, and compare this with that predicted by a computer program based on the principles of the TPM. Methods. This was a cross-sectional study of UF and [Na+](D) collected prospectively from dwells classified by length, glucose concentration and membrane transport characteristics. Solute transport, converted to area parameter and UF capacity, was measured on each occasion by the peritoneal equilibration test. These parameters, along with plasma [Na+], were entered into the computer model. Fixed values for other parameters, e.g. hydraulic conductance and lymphatic absorption and sump volume, were used. Results. A total of 1853 dwells from 182 patients [10% were on automated PD (APD)] were analysed. There was a high degree of correlation (r=0.83-95, P<0.001) between the observed and predicted values for UF, [Na+](D) and sodium removal across the full range of dwell categories. The model overpredicted UF as the net volume increased with increasing glucose concentration, independently of solute transport. This bias was not fully explained by the preferential use of hypertonic dialysate by patients with reduced UF capacity. The prediction of [Na+](D) described sodium sieving, which was overestimated in a small number of patients with UF failure. There were no discrepancies between continous ambulatory PD (CAPD) and APD patients. Conclusion. This analysis endorses the TPM as a description of membrane function, particularly in relation to sodium sieving and removal. The relationship between dialysate glucose concentration and achieved UF appears to be more complex; even accounting for extended time on treatment and reduction in the osmotic conductance in patients preferentially using hypertonic exchanges, further adjustments may be needed to account for the tendency to overestimate UF.
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| 2. |
- Asgeirsson, Daniel, et al.
(författare)
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Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
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| 3. |
- Asgeirsson, Daniel, et al.
(författare)
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Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats.
- 2006
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 291:5, s. 1083-1089
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Tidskriftsartikel (refereegranskat)abstract
- It is established that the glomerular filter sieves macromolecules based on their size, shape, and charge. Anionic proteins are thus retarded compared with their neutral or cationic counterparts. However, recent studies have indicated that charge effects are small, or even "anomalous," for polysaccharides. We therefore investigated the impact of charge on the glomerular permeability to polysaccharides by comparing sieving coefficients ({theta}; primary urine-to-plasma concentration ratio) for negatively charged, carboxymethylated (CM) FITC-Ficoll and FITC-dextran with their neutral counterparts. For these probes, {theta} were determined in anesthetized Wistar rats [269 ± 2.7 g (±SE; n = 36)], whose ureters were cannulated for urine sampling. The glomerular filtration rate was assessed using FITC-inulin. Polysaccharides were constantly infused, and after equilibration, urine was collected and a midpoint plasma sample was taken. Size and concentration determinations of the FITC-labeled polysaccharides were achieved by size-exclusion HPLC (HPSEC). For CM-Ficoll, {theta} was significantly increased (32 times at 55 Å) compared with that of uncharged Ficoll. A small increase in {theta} for CM-dextran compared with neutral dextran was also observed (1.8 times at 55 Å). In conclusion, negatively charged Ficoll relative to neutral Ficoll was found to be markedly hyperpermeable across the glomerular filter. Furthermore, negatively charged Ficoll was observed to be larger on HPSEC compared with its neutral counterpart of the same molecular weight. It is proposed that the introduction of negative charges in the "dendrimeric," cross-linked Ficoll molecule may alter its configuration, so as to make it more extended, and conceivably, more flexible, thereby increasing its glomerular permeability. charge barrier; capillary permeability; macromolecules; fractional clearance; reflection coefficients IT IS GENERALLY ACCEPTED THAT the glomerular filter discriminates among macromolecules based on their size, shape, and net charge (6, 8). With respect to charge, the permeability of anionic dextran sulfate was found to be reduced and that of cationic, diethylaminoethyl (DEAE) dextran to be increased compared with that of neutral dextran (6). However, more recent studies have indicated that sulfated dextran may be processed in the kidney (28) and desulfated during its renal passage (10), and furthermore, that it may bind to plasma proteins (17), and to membrane phospholipids (25), causing an artifactual reduction in the sieving coefficients ({theta}; i.e., the primary urine-to-plasma concentration ratios) of dextran sulfate. In addition, isolated glomerular basement membranes (GBM) have generally failed to show charge selectivity when probed with neutral and negatively charged Ficoll (7) or native (anionic) or cationized albumin (4). In line with these findings, Schaeffer et al. (26) were unable to find (in rats in vivo) any difference between glomerular {theta} to carboxymethylated (non-sulfated) dextran or to hydroxymethyl starch (HES), both negatively charged, and their neutral counterparts. Furthermore, the HES molecules showed lower {theta} for any given Stokes-Einstein (SE) radius (cf. Ficoll) than did dextran. It was concluded that the glomerular filtration barrier restricts the transport of polysaccharide macromolecules as a function of size and configuration whereas the presence or absence of negative charge does not play any role. Further supporting these results, Guimarães et al. (18) did not find a decrease in glomerular permeability to negatively charged, carboxymethylated (CM) Ficoll compared with uncharged Ficoll, confirming a previous observation by Greive et al. (16). Instead, they found a markedly increased glomerular permeability to CM-Ficoll. In contrast to the apparent inability of the glomerular filter to discriminate between polysaccharides of different charge, there is ample evidence that, indeed, the glomerular filter selects globular proteins based on their charge. Thus anionic proteins are retarded compared with neutral and cationic proteins, as extensively reviewed by Comper and Glasgow (9) and Venturoli and Rippe (29). The reason the glomerular capillary wall exhibits low discrimination ability with respect to differently charged polysaccharides, while being able to separate proteins of different molecular charge, is obscure. However, one clue to this enigma could be the fact that carbohydrates exhibit an extended molecular configuration, with a larger SE radius, compared with that for globular proteins, for any given molecular mass (19, 29). Such an extended configuration, conceivably, generates a more flexible (compressible) structure and hence increases the molecule's permeability through the glomerular filtration barrier (29). Charge modification of a polysaccharide may lead to a further increase in molecular extension, favoring an increased flexibility and, thereby, an increased solute permeability. Could the process of charge modification of the highly cross linked and "ellipsoid" molecules of Ficoll (19) lead to conformational alterations, with increased molecular extension, increasing their permeability compared with their uncharged counterparts? If so, would the linear, "random coil," structure of dextran make it less affected by conformational changes, and thereby less hyperpermeable, when negatively charged? The present study was performed to test this hypothesis by comparing glomerular sieving coefficients to negatively charged, CM-Ficoll and -dextran vs. their uncharged molecular equivalents.
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| 4. |
- Axelsson, Josefin, et al.
(författare)
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Effects of early endotoxemia and dextran-induced anaphylaxis on the size-selectivity of the glomerular filtration barrier in rats.
- 2009
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 296:2, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anaesthetized Wistar rats, the left ureter was catheterized for urine collection, while simultaneously, blood access was achieved. Endotoxemia was induced by Lipopolysaccharide (LPS) from E. Coli, and glomerular permeability assessed at 60, 90 (ENDO-(60)/90; n=7) and 120 min (ENDO-120; n=7). Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min (ANA-5; n=8) and 40 min (ANA-40; n=9). Sham animals, were followed for either 5 or 120 min. The glomerular sieving coefficients () to FITC-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). 2 h after start of the LPS infusion, but not at 60 or 90 min, for Ficoll70A had increased markedly (from 2.91 x 10(-5) +/- 6.33 x 10(-6) to 7.78 x 10(-5) +/- 6.21 x 10(-6) (P<0.001)). In anaphylaxis there was a large increase in for Ficolls >60 A in mol. radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter. Key words: capillary permeability, Ficoll, sieving coefficient, albumin.
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| 5. |
- Bentzer, Peter, et al.
(författare)
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Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat.
- 2003
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 20:5, s. 447-461
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.
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| 6. |
- Davies, Simon, et al.
(författare)
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The effects of low-sodium peritoneal dialysis fluids on blood pressure, thirst and volume status
- 2009
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 24:5, s. 1609-1617
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Tidskriftsartikel (refereegranskat)abstract
- Background. Poor ultrafiltration is associated with worse outcomes in peritoneal dialysis (PD) patients. This might in part reflect problems associated with salt and water excess. Increasing the diffusive component of peritoneal sodium removal using low-sodium PD fluids might have beneficial effects on blood pressure (BP), thirst and fluid status that could translate into clinical benefits. Methods. Using a multicentre, prospective, baseline controlled (1 month), non-randomized intervention (2 months) design, two novel solutions designed from predictions using the three-pore model were investigated. In group A ([Na+] = 115 mmol/l), the glucose (G) was increased to 2.0% to compensate for reduced osmolality whereas in group B ([Na+] = 102 mmol/l), it was unchanged (2.5%). Both solutions were substituted for one 3- to 5-h exchange per day and no change was made to the rest of the dialysis regime. Results. Ten patients in group A and 15 in group B completed the study. Both solutions resulted in significant increases (30-50 mmol/dwell) in diffusive sodium removal during the test exchanges, P < 0.001. Ultrafiltration was maintained in group A but reduced in group B. Ambulatory nocturnal mean BP fell in group A [93.1 +/- 10.6 mmHg (+/- SD) versus 85.1 +/- 10.2 mmHg, P < 0.05], but was stable in group B (95.4 +/- 9.4 versus 95.1.1 +/- 10.7 mmHg, NS). Thirst reduced independent of appetite and mood in both groups by 2 months, more markedly in group A. Indices of fluid status, including TBW by bioimpedance and D dilution also improved in group A, P < 0.05, whereas weight increased in group B. Conclusions. Increasing the diffusive component of sodium removal whilst maintaining ultrafiltration is associated with improvements in BP, thirst and fluid status. The lack of effect seen with uncompensated low-sodium dialysate suggests that these benefits cannot be achieved by manipulation of dialysate sodium removal alone. These observations provide valuable information of the design of future randomized studies to establish the clinical role for low-sodium dialysis fluids.
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| 7. |
- Dousdampanis, Periklis, et al.
(författare)
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Two icodextrin exchanges per day in peritoneal dialysis patients with ultrafiltration failure: one center's experience and review of the literature
- 2011
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Ingår i: International Urology and Nephrology. - : Springer Science and Business Media LLC. - 1573-2584 .- 0301-1623. ; 43:1, s. 203-209
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Tidskriftsartikel (refereegranskat)abstract
- At present, only one exchange of an icodextrin-based solution is recommended to increase peritoneal ultrafiltration (UF) during long-dwell exchanges in peritoneal dialysis (PD) patients with impaired UF. To review our experience with two icodextrin exchanges per day on net UF and body weight in PD patients with poor UF. Data were analyzed on nine patients with poor UF on chronic PD who were given two icodextrin exchanges per day for 6 months and had various clinical and biochemical parameters assessed monthly. Administration of icodextrin twice daily reduced the body weight in six of nine patients by an average of 2.9 +/- A 1.2 kg, a reduction that was maintained throughout the study; two patients gained 0.5 kg; and, in one patient, the measurements were inadequate. Mean blood pressure was reduced. Mean serum creatinine increased slightly. Serum sodium levels decreased from a mean baseline level of 134 +/- A 3 to 132 +/- A 4 mmol/L at three and six months. Among the diabetics in this group, average daily insulin requirements were 44 +/- A 35 units/day at baseline and 40 +/- A 23 units/day after 6 months. Hb1Ac levels remained stable throughout the study period. The use of two icodextrin exchanges per day reduced body weight in six of the nine patients and appeared to be safe. Long-term prospective studies are needed to assess the contribution of twice-daily icodextrin to the management of peritoneal dialysis patients with ultrafiltration failure and its long-term safety.
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| 8. |
- Jungner, Mårten, et al.
(författare)
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Blood-brain barrier permeability following traumatic brain injury.
- 2016
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Ingår i: Minerva Anestesiologica. - 1827-1596. ; 82:5, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brain edema and intracranial hypertension is deleterious after traumatic brain injury (TBI), but the underlying pathophysiology is complex and poorly understood. One major subject of controversy is the time course and extent of blood-brain barrier (BBB) dysfunction following trauma, and previous studies in humans have only provided semi-quantitative data. The objective of the present study was therefore to quantify changes in BBB-permeability in the early course of TBI, when brain edema is still evolving. METHODS: Sixteen non-consecutive brain trauma patients and two controls were included. Following i.v. injection of iohexol and CT perfusion scans, patients were scanned eight times from 4 to 25 minutes. Blood to brain transfer constant (Ki) for iohexol (molecular weight 821 D), reflecting permeability and available area for diffusion, was calculated offline by Patlak plot analysis of the enhancement curves of intracerebral large venous vessels and pericontusional brain parenchyma. RESULTS : In non-ischemic tissue surrounding contusions and hematomas Ki was increased 2-to 10-fold compared to normal tissue, reaching maximal values of 0.5 mL/min/100 g. In non-injured areas and in controls Ki was about 0.06 mL/min/100 g. The increase was more pronounced in the most severely injured patients, and was detectable within 24 hours after trauma and up to five days after. CONCLUSIONS: Our results suggest that traumatic brain injury is associated with early focal increases in small molecular BBB-permeability. The results indicate that in the injured brain, capillary hydrostatic and oncotic pressures may influence edema formation.
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| 9. |
- Lund, Ulla, et al.
(författare)
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Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys
- 2003
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 284:6, s. 1226-1234
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Tidskriftsartikel (refereegranskat)abstract
- The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs. glomerular filtration rate (GFR; Cr-51-EDTA clearance) in intact rats for radiolabeled myoglobin, kappa-dimer, neutral horseradish peroxidase (nHRP), neutral human serum albumin (nHSA), and native albumin (HSA). To obtain theta, glomerular tracer clearance, assessed from the 7- to 8-min kidney uptake of protein, was divided by the GFR. The data were fitted with a two-pore model of glomerular permeability, where the small-pore radius was 37.35 +/- 1.11(SE) Angstrom, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 . 10(6) cm. Although seemingly horizontal for nHRP and nHSA, the log theta vs. GFR curves showed slightly negative slopes for the proteins investigated in the GFR interval of 2-4.5 ml/min. Strong negative ( linear) correlations between ( log) theta and GFR were obtained for myoglobin (P = 0.002) and HSA (P = 0.006), whereas they were relatively weak for nHRP and nHSA and nonsignificant for kappa-dimer. theta for nHSA was markedly higher than that for HSA. In conclusion, there were no indications of increases in theta vs. GFR, as indicative of concentration polarization, for the proteins investigated at high GFRs. Furthermore, the glomerular small-pore radius assessed from endogenous (neutral) protein sieving data was found to be smaller than previously determined using dextran or Ficoll as test molecules.
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| 10. |
- Marchesini, Renato, et al.
(författare)
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In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions--I. Reflectance measurements
- 1991
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Ingår i: Photochemistry and Photobiology. - : Wiley. - 0031-8655 .- 1751-1097. ; 53:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Reflectance spectrophotometry from 400 to 800 nm on different cutaneous pigmented lesions, including primary and metastatic malignant melanoma, pigmented nevi, lentigo and seborrhoeic keratosis, has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of the different lesions manifest dissimilar patterns, particularly in the near IR region. Comparison of reflectance of nevi with that of malignant melanomas results in a highly significant difference (P less than 10(-6)) between the two samples. Though interpretation of the spectra remains difficult as a result of the complexity of the optical processes of scattering and absorption, our results suggest that a detailed analysis of the reflectance spectrum may give clinically useful information, and could be utilized as an aid in clinical diagnosis of cutaneous pigmented lesions, especially where malignant melanoma is concerned.
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