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Sökning: WFRF:(Breborowicz A)

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  • Pawlaczyk, K, et al. (författare)
  • Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation
  • 2008
  • Ingår i: The International journal of artificial organs. - : SAGE Publications. - 0391-3988 .- 1724-6040. ; 31:6, s. 535-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. Methods Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (μg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. Results LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/μL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-α, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2±5.9; LPS 0.01, 38.9±11.6; LPS 0.1, 43.0±5.9; LPS 1.0, 46.6±11.3; Control, 14.5±9.8; p<0.0005 for all LPS vs. Control). Conclusions The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-α, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.
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  • Yao, Q, et al. (författare)
  • Peroxisome proliferator-activated receptor-gamma agonists diminish peritoneal functional and morphological changes induced by bioincompatible peritoneal dialysis solution
  • 2006
  • Ingår i: Blood purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 24:5-6, s. 575-582
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> To evaluate if peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have a potential protective effect on the peritoneum changes induced by bioincompatible peritoneal dialysis (PD) solution in vivo. <i>Methods:</i> Male Wistar rats were dialyzed three times daily for 28 days with 1.36% Dianeal® (two groups: with (D+R) or without (D) rosiglitazone) or 1.36% Physioneal® (two groups: with (P+R) or without (P) rosiglitazone). Peritoneal transport of fluid and small solutes was assessed. Nine rats that did not receive dialysis served as controls. <i>Results:</i> Significant morphological changes were found in the D group compared with controls. Additional use of rosiglitazone in the D+R group resulted in less morphological changes and expression of collagen I as well as an increased drainage volume. The expression of VEGF was inhibited by rosiglitazone while no apparent effect was found regarding TGF/Smad pathway. <i>Conclusions:</i> The addition of rosiglitazone to standard dialysis fluids can maintain the peritoneal morphology and increase ultrafiltration in a PD rat model.
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  • Yao, Q, et al. (författare)
  • The role of the TGF/Smad signaling pathway in peritoneal fibrosis induced by peritoneal dialysis solutions
  • 2008
  • Ingår i: Nephron. Experimental nephrology. - : S. Karger AG. - 1660-2129. ; 109:2, s. E71-E78
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-β1/Smad signaling pathway in a chronic PD rat model. <i>Methods:</i> Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal® 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal® 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls. <i>Results:</i> The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-β1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-β1/Smad expression and less expansion of the submesothelial cell layer. <i>Conclusions:</i> Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-β1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism.
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  • Dubiel, M, et al. (författare)
  • Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy
  • 2005
  • Ingår i: Journal of Perinatal Medicine. - 1619-3997. ; 33:1, s. 17-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-alpha. (TNF-alpha) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies. Study design: TNF-alpha and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-alpha and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score. Results: TNF-alpha levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-alpha and IL-6 levels, P < 0.0001 and P < 0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-alpha and IL-6 levels. Abnormal uterine artery PI and the presence of a "notch" were also highly significantly related to TNF-alpha and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a "notch". Abnormal cerebro/placental ratios showed significant correlations to TNF-alpha and IL-6 levels. Conclusion: The present results suggest a strong correlation between levels of TNF-a and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.
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  • Ghosh, Gisela, et al. (författare)
  • Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications.
  • 2006
  • Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 19:9, s. 551-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Uterine artery Doppler is becoming a routine part of pregnancy surveillance in high-risk pregnancies. Which blood flow velocity waveform index to measure is debated and the 'notch' in early diastole is not widely accepted, as it is a subjective measure. The aim of the present study was to evaluate the different indices in the prediction of adverse outcome of pregnancies suspected for intrauterine fetal growth restriction (IUGR). Methods. Uterine artery blood flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance due to suspected IUGR. The median gestational age at examination was 38 weeks (range 25-42 weeks). Only cases having bilateral uterine artery notching were included in the evaluation. The uterine artery Doppler spectrum was analyzed for different indices, including evaluation of notch and end-diastolic velocities. Umbilical artery Doppler velocimetry was also performed. The outcome variables chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and abdominal delivery. ROC-curve calculations were used to compare the different indices. Results. The uterine artery blood velocity pulsatility index (PI) and resistance indices (RI) were the best predictors of adverse outcome of pregnancy. Apart from premature birth, the systolic/end-diastolic ratio was less predictive of adverse outcome. The indices including only diastolic blood velocities were the least predictive of adverse outcome. The group with notch velocity above end-diastolic velocity was compared with those having notch velocity below the end-diastolic velocity. No difference in outcome was seen between the two groups. Conclusions. RI and PI as measures of third trimester utero-placental vascular impedance are the best predictors of adverse outcome of IUGR-suspected pregnancies.
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  • Korszun, P, et al. (författare)
  • Fetal superior mesenteric artery blood flow velocimetry in normal and high-risk pregnancy
  • 2002
  • Ingår i: Journal of Perinatal Medicine. - 1619-3997. ; 30:3, s. 235-241
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim: To record blood flow velocimetry in the fetal superior mesenteric artery in normal pregnancy and to evaluate if blood flow recordings in the vessel might predict adverse outcome in high-risk pregnancy. Methods: The fetal superior mesenteric artery blood velocimetry was recorded in a cross sectional manner in 75 normal pregnancies between 27 and 41 weeks of gestation. Reference curves were performed for pulsatility and resistance indices. The superior mesenteric artery was also located in 48 singleton pregnancies complicated by pregnancy-induced hypertension and/or intra-uterine growth retardation. Middle cerebral artery, umbilical artery and vein and uterine artery velocimetry were also recorded. Results: Superior mesenteric artery PI and RI values expressed an increase in resistance to blood flow with gestational age after 32 weeks of gestation. In all except eight high-risk pregnancies the fetal mesenteric artery PI values were within normal range. Among the pregnancies with absent or reversed blood flow in the umbilical artery, all had abnormal mesenteric artery pulsatility index (PI) (> 97.5(th) percentiles), one fetus died intrauterine and two others died after delivery due to prematurity, growth retardation and necrotizing enterocolitis. In the remaining fetuses with increased mesenteric artery PI, necrotizing enterocolitis was diagnosed in three cases. Conclusions: Increased vascular resistance in the mesenteric artery might be a late sign of fetal circulation redistribution and frequently related to necrotizing enterocolitis in the newborn.
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  • Pawlaczyk, K, et al. (författare)
  • Animal Models of Peritoneal Dialysis: Thirty Years of Our Own Experience
  • 2015
  • Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2015, s. 261813-
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental animal models improve our understanding of technical problems in peritoneal dialysis PD, and such studies contribute to solving crucial clinical problems. We established an acute and chronic PD model in nonuremic and uremic rats. We observed that kinetics of PD in rats change as the animals are aging, and this effect is due not only to an increasing peritoneal surface area, but also to changes in the permeability of the peritoneum. Changes of the peritoneal permeability seen during chronic PD in rats are comparable to results obtained in humans treated with PD. Effluent dialysate can be drained repeatedly to measure concentration of various bioactive molecules and to correlate the results with the peritoneal permeability. Additionally we can study inin vitroconditions properties of the effluent dialysate on cultured peritoneal mesothelial cells or fibroblasts. We can evaluate acute and chronic effect of various additives to the dialysis fluid on function and permeability of the peritoneum. Results from such study are even more relevant to the clinical scenario when experiments are performed in uremic rats. Our experimental animal PD model not only helps to understand the pathophysiology of PD but also can be used for testing biocompatibility of new PD fluids.
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  • Pawlaczyk, K, et al. (författare)
  • Effects of bicarbonate/lactate dialysis solution on the inflammatory response of spontaneous peritonitis in rats undergoing chronic peritoneal dialysis
  • 2009
  • Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 28:3, s. 200-208
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> We evaluated the incidence of spontaneous peritonitis as well as the local inflammatory response and macroscopic changes in the peritoneum during the use of a bicarbonate/lactate-buffered (P) solution in comparison to conventional (D) solutions in rats on chronic peritoneal dialysis. <i>Methods:</i> Sixty-three male Wistar rats were implanted with peritoneal catheters. After 7 days, the animals were randomly divided into 2 experimental groups (32 rats in D, 31 rats in P) and infused twice daily over the following 4 weeks. <i>Results:</i> After 14 and 23 days, rats dialyzed with D had a higher peritonitis rate than those dialyzed with P. The median number of days until peritonitis occurred was 22 days for the rats in the D group and 29 days for the rats in the P group. Spontaneously infected rats dialyzed with the D solution had higher scores for adhesion formation. <i>Conclusions:</i> In this animal model, dialysis with P delayed the time to the 1st infection, reduced the overall peritonitis rate and reduced peritonitis-associated peritoneal adhesion formation during chronic peritoneal dialysis.
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