Intraperitoneal Hyaluronan Administration in Conscious Rats: Absorption, Metabolism, and Effects on Peritoneal Fluid Dynamics

2001 ◽  
Vol 21 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Alicja Polubinska ◽  
Krzysztof Pawlaczyk ◽  
Malgorzata Kuzlan–Pawlaczyk ◽  
James Moberly ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Total Protein ◽  
Peritoneal Fluid ◽  
Intraperitoneal Administration ◽  
Blood Levels ◽  
Interstitial Tissue ◽  
Conscious Rats ◽  
Peritoneal Tissue ◽  
Peritoneal Permeability

Background Hyaluronan (HA) is a major component of interstitial tissue that participates in fluid homeostasis, response to inflammation, and wound healing. Previous studies have shown that intraperitoneal administration of HA can affect peritoneal fluid transport during short peritoneal dialysis exchanges in anesthetized rats. We sought to investigate the effect of high molecular weight HA on peritoneal permeability in conscious rats during dialysis exchanges up to 8 hours in duration. In addition, we sought to investigate the absorption of HA from the peritoneal cavity, its accumulation in peritoneal tissues, and its metabolism in normal and uremic rats. Methods Experiments were performed on male Wistar rats infused with 30 mL peritoneal dialysis solution (Dianeal, Baxter Healthcare; Castelbar, Ireland) containing 10 mg/dL HA or with Dianeal alone (control). Peritoneal fluid removal (net ultrafiltration), permeability to glucose, creatinine, and total proteins, and tissue and blood levels of HA were determined in separate groups of rats at 1, 2, 4, 6, and 8 hours after intraperitoneal infusion. Hyaluronan appearance and disappearance from plasma were also studied for 24 hours in separate groups of normal and uremic rats. Results Net ultrafiltration was significantly greater (27%) in rats infused with HA at 4, 6, and 8 hours ( p < 0.01) compared to controls. Transperitoneal equilibration of protein was reduced by 27% ( p < 0.001) at 4 hours and by 30% ( p < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clearance of creatinine increased by 27% ( p < 0.01), whereas the clearance of total protein decreased by 27% ( p < 0.005). After 8 hours, 25.7% ± 3.1% of the administered HA was absorbed from the peritoneal cavity, peritoneal tissue HA concentration was increased by 117% ( p < 0.001), and plasma HA levels increased by 435% ( p < 0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal administration in both healthy and uremic rats. Conclusions Hyaluronan added to dialysis fluid is absorbed from the peritoneal cavity and accumulates in peritoneal tissues. Hyaluronan supplementation produces changes in peritoneal permeability, leading to higher net ultrafiltration and peritoneal creatinine clearance, whereas total protein clearance decreases. The HA that is absorbed from the peritoneal cavity appears to be rapidly metabolized in both healthy and uremic rats.

scholarly journals Hyaluronan decreases peritoneal fluid absorption in peritoneal dialysis.

1997 ◽  
Vol 8 (12) ◽  
pp. 1915-1920
Author(s):  
T Wang ◽  
C Chen ◽  
O Heimbürger ◽  
J Waniewski ◽  
J Bergström ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Protein Transport ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Fluid Absorption ◽  
Sprague Dawley ◽  
Transfer Coefficients ◽  
Fluid Removal ◽  
Dialysis Solution

Hyaluronan, exhibiting a high resistance against water flow, acts in the tissue as a barrier against rapid changes in water content. To test whether hyaluronan has any effect on the peritoneal fluid and solute transport, and, in particular, on the peritoneal fluid absorption, a 4-h dwell study with an intraperitoneal volume marker (radiolabeled human serum albumin [RISA]) was conducted in 21 male Sprague Dawley rats (three groups, seven rats in each group). Each rat was injected intraperitoneally with 25 ml of 1.36% glucose solution alone (control group), with 0.005% hyaluronan (HA1 group), or with 0.01% hyaluronan (HA2 group). Dialysate and blood samples were taken frequently for analyses of fluid and solute (urea, glucose, and protein) transport. The intraperitoneal volume was calculated from the dilution of RISA with a correction for RISA disappearance from the peritoneal cavity. This study shows that adding hyaluronan to peritoneal dialysis solution significantly (P < 0.01) increased the net peritoneal fluid removal, mainly due to a significant decrease in the peritoneal fluid absorption rate (P < 0.01). The diffusive mass transfer coefficients for glucose, urea, and protein did not differ between the three groups. The peritoneal clearance of urea increased significantly in the two hyaluronan groups compared with the control group, due to the increased net fluid removal in the hyaluronan groups. These results suggest that intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption.

Variability of Peritoneal Protein Loss in Diabetic and Nondiabetic Patients on Continuous Ambulatory Peritoneal Dialysis

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 242-244 ◽  
Author(s):  
Sophia Spaia ◽  
Fotini Christidou ◽  
Panayotis Pangidis ◽  
Thomas Tsoulkas ◽  
Michalis Pazarloglou ◽  
...  
Keyword(s):  
Body Weight ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Total Protein ◽  
Peritoneal Fluid ◽  
Protein Loss ◽  
Glucose Levels ◽  
Short Period ◽  
Group A ◽  
Group B

In order to evaluate the Influence of diabetes mellitus on peritoneal membrane permeability, we studied the peritoneal protein loss In two groups of patients. Group A consisted of 16 patients (9 nondlabetics and 7 diabetics) who were In the first month of treatment on continuous ambulatory peritoneal dialysis (CAPO). Group B consisted of 13 patients (7 nondlabetics and 6 diabetics) who had been on CAPO for approximately 15 months. In both groups we measured the body weight, serum total protein, albumin, and total protein, urea, and glucose In the peritoneal fluid. We did not find any difference In groups A and B between diabetics and nondlabetics as far as the estimated parameters were concerned. Age, body weight, serum biochemistry, and protein and urea content In peritoneal fluid were similar, when group A was compared to group B. Patients of group B hed on average higher protein losses than those who had been on the method for a short period (mean 7.9 g/dL, vs 6.09 g/dL). Six patients were followed for over 15 months and were found to have significantly Increased protein losses (p=0.02). Glucose levels In peritoneal fluid were significantly lower In patients In group B, p<0.05 (mean 51.8 g/dL vs 37.1 g/dL). Peritoneal protein loss does not seem to differ between diabetic and nondiabetic patients with end-stage renal disease treated with CAPO, at any given time of the treatment. We observed an Increase In protein loss In some patients and a tendency to Increase the protein loss In others. This, along with the fall In glucose levels, might reflect progressive alterations In structure and permeability of the elements Involved In peritoneal transport, and It should receive further evaluation.

scholarly journals Concomitant bidirectional transport during peritoneal dialysis can be explained by a structured interstitium

2016 ◽  
Vol 310 (11) ◽  
pp. H1501-H1511 ◽  
Author(s):  
Joanna Stachowska-Pietka ◽  
Jacek Waniewski ◽  
Michael F. Flessner ◽  
Bengt Lindholm
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Phase Structure ◽  
Animal Studies ◽  
Theoretical Explanation ◽  
Distributed Model ◽  
Two Phase ◽  
Tissue Hydration ◽  
Peritoneal Tissue ◽  
Bidirectional Transport

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data.

N-Acetylglucosamine Changes Permeability of Peritoneum during Chronic Peritoneal Dialysis in Rats

1998 ◽  
Vol 18 (2) ◽  
pp. 217-224 ◽  
Author(s):  
George Wu ◽  
Katarzyna Wieczorowska Tobis ◽  
Alicja Polubinska ◽  
Katarzyna Korybalska ◽  
Violetta Filas ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Blood Cell ◽  
Cell Count ◽  
Total Protein ◽  
Glucose Solution ◽  
Chronic Peritoneal Dialysis ◽  
Dialysis Fluid ◽  
Blood Cell Count ◽  
Dialysis Solution ◽  
Peritoneal Permeability

Objective To evaluate the effect of supplementation of dialysis fluid with N-acetylglucosamine (NAG) on the permeability of peritoneum during chronic peritoneal dialysis in rats. Design Experiments were performed on rats with surgically implanted peritoneal catheters. Dialysis solution [DianeaI1.5% (Baxter, Deerfield, IL, U.S.A.) supplemented with either NAG 50 mmol/L or glucose 50 mmol/L (control)] was infused intraperitoneally twice, every day, for 8 weeks. Peritoneal equilibration tests (PET) were performed in all animals at the beginning of the study and after 8 weeks of dialysis. Additionally, at the end of each week, dialysis solution infused in the morning was drained after 4 hours of intraperitoneal dwell. White blood cell count, creatinine, and total protein concentrations were measured in the effluent dialysate. After 8 weeks of dialysis, the morphology of the peritoneum was studied. Results In rats exposed to dialysis fluid supplemented with NAG, peritoneal permeability to creatinine and proteins was reduced when compared to animals dialyzed with glucose solution. In NAG treated animals, staining with alcian blue for polyanions in the peritoneal interstitium was significantly stronger than in rats dialyzed with glucose solution. Conclusions Chronic peritoneal dialysis with dialysis solution supplemented with N-acetylglucosamine causes accumulation of glycosaminoglycans in the peritoneal interstitium, which results in a change of peritoneal permeability.

Clearance of Tracer Albumin from Peritoneal Cavity to Plasma at Low Intraperitoneal Volumes and Hydrostatic Pressures

1998 ◽  
Vol 18 (5) ◽  
pp. 497-504 ◽  
Author(s):  
Qing Zhu ◽  
Ola Carlsson ◽  
Bengt Rippe
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Fluid Volume ◽  
Free Fluid ◽  
Annual Conference ◽  
Lymphatic Absorption ◽  
Tissue Samples ◽  
Essentially Normal ◽  
Peritoneal Tissue ◽  
Tracer Distribution

Objective To assess the clearance of radiolabeled tracer albumin (RISA) from peritoneal cavity to plasma (CI → P) in rats under essentially “normal” conditions, that is, when intraperitoneal hydrostatic pressure (IPP) is subatmospheric and the intraperitoneal (IP) “free” fluid volume (IPV) is low. Methods A volume of 0.3 mL of RISA was injected IP into anesthetized Wistar rats (wt = 300 g) when the IPV was approximately 2 mL (normal) or the IPV was approximately 10 mL, and IPP was either -1.8 mmHg (normal) or +1.5 mmHg (produced by an external cuff). Plasma samples (25 μL) were obtained repeatedly during the dwell, which lasted 30 300 min, after which the peritoneal cavity was opened to recover the IPV and residuallP RISA activity. The CI → P was assessed as the mass transfer of RISA into plasma, occurring per unit time,-divided by the calculated mean IP RISA concentration (CD). The interstitial RISA space was measured as the mass of RISA accumulated, per unit tissue weight, in peritoneal tissue samples divided by the CD. Results A markedly lower CI → P (2.47 ± 0.67 μL/min), as well as total RISA clearance out of the peritoneal cavity (CI), was found under “normal” conditions (an IPV of approximately 2 mL and an IPP of approximately -1.8 mmHg) compared to the situation during peritoneal dialysis (an IPV of approximately 20 mL and an IPP of +1 mmHg). Furthermore, the interstitial RISA space increased linearly over time even at negative IPPs and at an unchanging peritoneal interstitial fluid volume. At a low (normal) IPV the CI → P did not increase significantly with elevating IPP, and increased only marginally when tracer distribution was improved by artificial vibration of the rats. However the CI → P increased when larger volumes were infused to increase the totallPV. Conclusions It is concluded that the CI → P and CI at low IPPs and IPVs are not as high as during peritoneal dialysis. Increases in CI → P were, however, coupled to increases in IPV. This highlights the importance of the IPV per se and of a sufficient IP tracer distribution for direct lymphatic absorption to be efficient. This study was presented in part at the XVIth Annual Conference on Peritoneal Dialysis, Denver, Colorado, U.S.A., 1997 (33).

Bidirectional peritoneal transport of immunoglobulin in rats: compartmental kinetics

1992 ◽  
Vol 262 (2) ◽  
pp. F275-F287 ◽  
Author(s):  
M. F. Flessner ◽  
R. L. Dedrick ◽  
J. C. Reynolds
Keyword(s):  
Peritoneal Cavity ◽  
Total Protein ◽  
Protein Transport ◽  
Absorbed Dose ◽  
Surrounding Tissue ◽  
Lymphatic Transport ◽  
Protein Loss ◽  
Tissue Concentrations ◽  
Peritoneal Tissue ◽  
High Concentrations

Protein transport to and from fluid in the peritoneal cavity is observed during clinical procedures. Dialysate osmolality is a major determinant of net fluid flux into the cavity. We carried out experiments in rats to determine the plasma, peritoneal, and tissue concentrations of immunoglobulin (Ig) G resulting from either intravenous (iv) or intraperitoneal (ip) administration during hypertonic or isotonic dialyses. After iv injection of IgG, overall mass transfer into the cavity was not affected by the osmolality. After ip injection, tissue concentrations were dependent on the dialysis duration. Protein absorption from the hypertonic dialysate into the surrounding tissue was quantitatively less than the absorption from an isotonic dialysis solution at 20 min. By 200 min, total protein transport was not affected by dialysate osmolality. Lymphatic transport to the plasma amounted to 20–25% of the total protein loss from the peritoneal cavity; approximately 60% of the absorbed dose was found in tissues surrounding the cavity at both 20 and 200 min, with particularly high concentrations in parietal areas. We conclude that immunoglobulin transport in the peritoneal tissue, resulting from either iv or ip injection, is influenced by route of administration but is little affected by dialysate osmolality. Peritoneal absorption of proteins occurs directly into the surrounding tissue interstitial space as a result of hydrostatic pressure-driven convection and diffusion.

Peritoneal Fluid and Tracer Albumin Kinetics in the Rat. Effects of Increases in Intraperitoneal Hydrostatic Pressure

1995 ◽  
Vol 15 (2) ◽  
pp. 118-128 ◽  
Author(s):  
EL Rasheid Zakaria ◽  
Bengt Rippe
Keyword(s):  
Peritoneal Dialysis ◽  
Hydrostatic Pressure ◽  
Peritoneal Cavity ◽  
Peritoneal Fluid ◽  
Loss Rate ◽  
Dry Weight ◽  
Radioactive Tracer ◽  
Fluid Loss ◽  
Abdominal Muscles ◽  
Edema Formation

Objectives To study the peritoneal fluid loss rate, the clearance (CI) of radioactive tracer albumin (RISA) eliminated from the peritoneal cavity (PC), as well as the peritoneal-to-plasma RISA clearance (CI -+ P) during acute peritoneal dialysis (PD) at large elevations in intraperitoneal hydrostatic pressure (IPP). Design Experimental study in anesthetized Wistar rats. Methods The intraperitoneal volume (IPV) was assessed using RISA dilution, correcting for the RISA CI from the PC. Volume recovery at termination of the dwells was obtained using graduated cylinders and preweighed gauze tissues. Measurements of CI and CI -+ P were obtained by repeated micro-sampling of dialysate and plasma, respectively. The IPP was continuously measured, and could be varied by external concentric abdominal compression using an inflatable cuff. On termination of the experiments, samples from tissues lining the PC were analyzed with respect to their content of RISA and edema, the latter being assessed from wet/dry weight ratios. Results At 2 mm Hg of IPP (control) the RISA CI was 27.1:1:2.0(:1:SE)μL.min-l, whereas CI→ Pwasonly 8.07:1:0.67 μL.min-l, at a total fluid loss rate of 10.1:1:5.4μL.min-1 for 1.36% Dianeal. At an IPP of 14 mm Hg, the CI increased to 55.3±4.1 μL.min -1 and the peritoneal fluid absorption rate was 34.4±5.6 μL.min -l, whereas CI -+ P was just moderately increased as compared to control (11.2:1:1.4 μL. min -I). Furthermore, a pleural effusion of 1.16:1:0.08 mL was detectable at elevated IPPs. The degree of edema formation in the anterior abdominal muscles (AAM) and the diaphragm (DIA) was largely insignificant during 150 min at 2 mm Hg of IPP, but increased markedly at 14 mm Hg, as did the RISA uptake to the AAM and DIA. The discrepancy between CI and CI -+ P was largely accounted for by tracer entrance into tissues lining the peritoneal cavity, mainly the AAM. Conclusions At a nearly unchanging capillary Starling equilibrium, the losses of fluid and of RISA from the PC were markedly elevated at increased IPPs. However, the RISA clearance to the plasma appeared to be only moderately altered at elevated IPP and represented only a minor fraction of the RISA clearance out of the PC. Tissues lining the PC apparently act as a variable ‘sink’ for intraperitoneal proteins and fluid during peritoneal dialysis (PD).

A Chronic Inflammatory Infusion Model of Peritoneal Dialysis in Rats

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 368-372 ◽  
Author(s):  
Peter J. Margetts ◽  
Martin Kolb ◽  
Lisa Yu ◽  
Catherine M. Hoff ◽  
Jack Gauldie
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Gene Transfer ◽  
Peritoneal Fluid ◽  
Transforming Growth Factor ◽  
Membrane Damage ◽  
Intraperitoneal Administration ◽  
Peritoneal Membrane ◽  
Ultrafiltration Failure ◽  
Physiologic Saline

Objectives Peritoneal membrane changes are related to daily exposure to non physiologic dialysate and recurrent acute inflammation. We modified a daily infusion and inflammation model and evaluated it for fibrotic and angiogenic features. The feasibility of adenovirus-mediated gene transfer in the model was also assessed. Methods Peritoneal catheters were implanted in rats. Over a period of 4 weeks, the animals received a daily infusion of Dianeal 4.25% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) with an initial three doses of lipopolysaccharide (LPS) or physiologic saline. Peritoneal fluid was assayed for transforming growth factor beta (TGFβ) and vascular endothelial growth factor (VEGF). Animals were humanely killed at week 5. Net ultrafiltration was then measured, and tissue samples were immunostained for factor VIII. Mesenteric tissue was assayed for hydroxyproline content. Adenovirus-mediated gene transfer of β-galactosidase was assayed by intraperitoneal administration of the virus, 4 days before the end of the experiment. Results Animals treated with either Dianeal or physiologic saline showed peritoneal membrane thickening and increased vascularity. Fibrosis was demonstrated by increased hydroxyproline concentration. Ultrafiltration was impaired. We found increased concentrations of VEGF and TGFβ in the peritoneal fluid of animals treated with LPS and daily infusion. Adenovirus-mediated gene transfer to the peritoneal membrane was demonstrated in the model. Conclusions Exposure to LPS and daily Dianeal or physiologic saline leads to peritoneal fibrosis and neoangiogenesis. Vascularization and glucose transport correlate with ultrafiltration failure. The present animal model mimics changes seen in humans on peritoneal dialysis and may be valuable for evaluating short-term interventions to prevent membrane damage.

CHANGES IN VOLUME, TOTAL PROTEIN AND OVARIAN STEROID CONCENTRATIONS OF PERITONEAL FLUID THROUGHOUT THE HUMAN MENSTRUAL CYCLE

1978 ◽  
Vol 76 (1) ◽  
pp. 123-133 ◽  
Author(s):  
J. B. MAATHUIS ◽  
P. F. A. VAN LOOK ◽  
E. A. MICHIE
Keyword(s):  
Menstrual Cycle ◽  
Peritoneal Cavity ◽  
Total Protein ◽  
Peritoneal Fluid ◽  
Mean Value ◽  
Total Protein Content ◽  
Ovarian Activity ◽  
Ovarian Steroid ◽  
Normal Women ◽  
Human Menstrual Cycle

SUMMARY Peritoneal fluid was aspirated during laparoscopy from normal women at various stages of the menstrual cycle. The volume of the fluid was found to be influenced by the stage of the cycle, rising from an early proliferative mean value of 0·8 ml to a mean volume of 18·7 ml after ovulation and decreasing again to a mean volume of 5·4 ml in the late secretory phase. The mean volume of peritoneal fluid obtained from women using the contraceptive pill was 0·8 ml, whereas only negligible amounts of fluid were aspirated at laparotomy from the peritoneal cavity of men. Despite marked changes in volume, the total protein content of the peritoneal fluid (± 60% of the concentration measured in plasma) remained fairly constant throughout the cycle, although a slightly, but significantly, lower value was found in the late proliferative phase. After ovulation the concentration of oestradiol and progesterone in the peritoneal fluid was higher than in plasma in the majority of cases, suggesting that some follicular fluid had drained into the peritoneal cavity at that time. Progesterone, in contrast to oestradiol, was also found in higher concentrations in peritoneal fluid than in plasma before ovulation. These results suggest that the volume and ovarian steroid concentration of peritoneal fluid are influenced by cyclic ovarian activity. At least two mechanisms may account for these observations: changes possibly effected by oestradiol in vascular permeability leading to a change of inflow and outflow equilibrium at the level of the peritoneal membranes and ovarian–peritoneal transfer of fluid after and possibly also before follicular rupture.

scholarly journals Pharmacokinetics of Intraperitoneal and Intravenous Fosfomycin in Automated Peritoneal Dialysis Patients without Peritonitis

2012 ◽  
Vol 56 (7) ◽  
pp. 3992-3995 ◽  
Author(s):  
Selma Tobudic ◽  
Peter Matzneller ◽  
Brigitte Stoiser ◽  
Judith Maria Wenisch ◽  
Markus Zeitlinger ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Intravenous Administration ◽  
Peritoneal Fluid ◽  
Intraperitoneal Administration ◽  
Systemic Exposure ◽  
Intravenous Dose ◽  
Serum Concentrations ◽  
Automated Peritoneal Dialysis ◽  
Dialysis Patients ◽  
Maximum Serum

ABSTRACTBlood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

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