| 1. |
- Bernal, Ximena E., et al.
(author)
-
Empowering Latina scientists
- 2019
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
-
Journal article (other academic/artistic)
|
|
| 2. |
- Davies, Simon J., et al.
(author)
-
Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange
- 2008
-
In: NEPHROLOGY DIALYSIS TRANSPLANTATION. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:9, s. 2982-2988
-
Conference paper (peer-reviewed)abstract
- Background. Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumor necrosis factor-a, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular Volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. Methods. 50 patients were randomized to either 2,27% glucose or icodextrin (n = 28) ford long exchange following a month run in. Blood samples were obtained at - 1, 0, 3 and 6 months, coincident with measurements Of urine volume and fluid status. Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine Volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007. in patients randomized to icodextrin, but not glucose. There were no relationships between fluid Status and any inflammatory markers at any point of the Study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated: the only predictor of between-patient variability oil multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily Ultrafiltration, urine volume, fluid or inflammatory status. Conclusions. This analysis supports observational data that changes in fluid status are associated with changes ill urine volume. Icodextrin was not associated with a greater fall ill urine Output despite its larger effect on ECFv Changes ill fluid status Could not be explained or did not appeal to influence systemic inflammation. Nor call they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.
|
|
| 3. |
- Garcia Lopez, Elvia
(author)
-
Icodextrin metabolism in peritoneal dialysis : clinical and experimental studies
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- Icodextrin is a glucose polymer which is used as osmotic agent to provide sustained ultrafiltration (UF) during the long (8-16 hours) dwell in end-stage renal disease patients undergoing peritoneal dialysis (PD). The aims of this thesis were to study: the metabolism of icodextrin in the peritoneal cavity and in the circulation of PD patients and non-uremic rats, the role of alpha-amylase in its hydrolysis, and the rate of breakdown of a synthetic maltoheptaose (G7) ex vivo which we propose as a novel measure of amylase mediated oligosaccharide metabolism. Study I. Gel-filtration HPLC was applied to determine high and low molecular weight icodextrin molecules in dialysate and plasma from PD patients using glucose solution or icodextrin (after the first dwell or chronically). Total hydrolysis of the samples was used to validate the results. 39 % of the infused icodextrin was absorbed from the peritoneal cavity during the long dwell. The plasma concentration of icodextrin metabolites was significantly higher and alpha-amylase activity significantly lower in the icodextrin groups. Study II. An assay for measurement of total alpha-amylase activity in serum containing icodextrin degradation products was validated. The study demonstrated that the low values of plasma alpha-amylase activity in PD patients using icodextrin are correctly determined. Study III. In 23 non-uremic rats undergoing chronic PD using either glucose- or icodextrinbased dialysis solutions, a 4-hour dwell with icodextrin was performed twice, at days 10 and 21. There was a significant decrease in amylase activity in plasma (which is much higher than in humans) and an increase in dialysate. About 60 % of the infused icodextrin was absorbed from the peritoneal cavity at the end of the dwell. No icodextrin metabolites were detected in plasma at the end of the dwell. Study IV. The rate of degradation of G7 in plasma from healthy controls, and PD patients using only glucose solution or glucose in combination with icodextrin was investigated ex vivo. Samples were spiked with G7 and/or synthetic amylase, and incubated 4 hours at 37oC. The G7 degradation rate was lower in plasma from icodextrin patients but it was also reduced in PD patients using glucose, in spite of the higher amylase activity, as compared with the controls. This suggests that the amylase mediated carbohydrate metabolism is reduced in PD patients. It is possible that this could contribute to reduced hyperglycemic changes, especially in patients using icodextrin. Study V. When investigating also pre-dialysis (PreD) and hemodialysis (HD) patients, we found that the rate of degradation of G7 did not differ from the controls. Amylase activity was increased in the PreD, HD and GLU patients, and decreased in the ICO patients. The rate of G7 degradation per unit of amylase activity was reduced in PreD and GLU patients. The rate of G7 degradation was related to the endogenous amylase activity. These findings suggest that the amylase mediated oligosaccharide metabolism is altered in uremic patients, although this needs to be confirmed in larger studies. Study VI. The relationship between the efficacy of icodextrin in changing UF, fluid status and residual urine volume versus the concentration of plasma icodextrin metabolites was investigated. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily UF, urine volume, fluid or inflammatory status. Icodextrin was not associated with a greater fall in urine output despite its larger effect on the volume of extra-cellular fluid.
|
|
| 4. |
- García López, Elvia
(author)
-
Icodextrin metabolism in peritoneal dialysis : clinical and experimental studies
- 2005
-
Licentiate thesis (other academic/artistic)abstract
- Icodextrin (ICO, or polyglucose) is an effective osmotic agent for peritoneal dialysis (PD) patients (pts). ICO is a soluble polymeric form of glucose with an average molecular 'weight range from 13,000 to 19,000 dalton. Glucose is absorbed from the peritoneal cavity by diffusion. For ICO, however, the diffusive transport is limited, and absorption occurs primarily by convective transport. As a result the osmotic pressure created by ICO is relatively constant and ultrafiltration (UF) is sustained throughout a long dwell. Approximately 20 % to 40 % of the administered ICO is absorbed from the peritoneal cavity and is metabolized by alpha-amylase to yield ICO metabolites. The total amylase activity in plasma is reported to be reduced in ICO users due to both interference with the substrate and a possible real decreased. The aim of this study was to use HPLC with a modem gel-filtration media to determine high (HMW) and low (LMW) molecular weight ICO molecules in dialysate and plasma in P1) pts on treatment with ICO, to investigate ICO metabolism in plasma and dialysate, and to investigate possible relationships between the production of these compounds and alpha-amylase activity in serum. Similar studies were conducted in non-uremic rats undergoing chronic PD. Paper I. We evaluated the feasibility of a gel-filtration HPLC method for the determination of HMW and LMW ICO molecules in dialysate and plasma in PD pts, and to validate the results, samples were exposed to enzymatic hydrolysis. Absorption of ICO from the peritoneal cavity during the long dwell was 39 % of the initial amount. In dialysate, the largest HMW fractions decreased, whereas the middle molecules and LMW metabolites showed a relative increase. The plasma concentration of ICO metabolites was significantly higher and alpha-amylase activity significantly lower, in ICO groups. Paper II. To validate an assay for measurement of total alpha-amylase activity in serum containing ICO degradation products, three experiments were performed: 1) Supplementation of ICO up to 75 % of ICO did not interfere with the alpha-amylase assay. 2) Supplementation of synthetic alphaamylase: synthetic alpha-amylase was fully recovered. 3) Altering the concentration of the assay's substrate; interference of ICO could be shown when the assay was dramatically modified. This study shows that true values of alpha-amylase can be measured in samples containing ICO degradation products. Paper III. alpha-Amylase activity in plasma and dialysate, and the degradation of ICO during chronic PD was investigated in 23 nonuremic rats with implanted peritoneal catheter. A 4-hour dwell with ICO solution was performed twice, at days 10 and 21. Plasma samples were taken at 0 time and at the end of the dwell, and dialysate samples at 3, 15, 30, 60, 90, 120, and 240 min. a-alpha-Amylase OBS activity was much higher in rats than in humans. ICO metabolism was not influenced by chronic exposure to ICO. The rat is not an ideal species to study ICO metabolism; however, for certain aspects of ICO metabolism such as the intraperitoneal metabolism, may be useful. We conclude that accurate analysis of HMW fractions in dialysate and LMW ICO metabolites in plasma and dialysate can be achieved by gelfiltration HPLC with two different columns. This method can be used to study the complex pattern of changes of ICO and its metabolites in plasma and dialysate in PD pts, due to the combined impact of alpha-amylase activity, and diffusive and convective transport.
|
|
| 5. |
- Morelle, Johann, et al.
(author)
-
Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane
- 2018
-
In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 29:7, s. 1875-1886
-
Journal article (peer-reviewed)abstract
- Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.
|
|
