| 1. |
- Bryland, Anna, et al.
(författare)
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Infusion fluids contain harmful glucose degradation products.
- 2010
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; May 4, s. 1213-1220
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients.
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| 2. |
- Erixon, Martin, et al.
(författare)
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3,4-dge in peritoneal dialysis fluids cannot be found in plasma after infusion into the peritoneal cavity.
- 2008
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 28:3, s. 277-282
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucose degradation products (GDPs) are important in the outcome of peritoneal dialysis (PD) treatment. 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic GDP found in conventionally manufactured fluids and may, in addition, be recruited from 3-deoxyglucosone (3-DG). It is not known what happens with those GDPs in patients during PD. The aim of this study was to investigate if the 3,4-DGE and 3-DG in PD fluids can be found in plasma during treatment. DESIGN: PD patients were dialyzed with a conventional PD fluid containing 43 mumol/L 3,4-DGE and 281 mumol/L 3-DG. Parallel experiments were performed in rats as well as in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 mumol/L 3,4-DGE and 200 mumol/L 3-DG. RESULTS: The concentration of 3,4-DGE in the peritoneum decreased at a much higher rate than 3-DG during the dwell. 3,4-DGE was not, however, detected in the plasma of patients or rats during dialysis. The concentration of 3-DG in plasma peaked shortly after infusion of the fluid to the peritoneal cavity. The concentration of 3,4-DGE during experimental incubation in plasma decreased rapidly, while the concentration of 3-DG decreased only 10% as rapidly or less. CONCLUSION: 3,4-DGE could not be detected in plasma from either PD patients or rats during dialysis. This is presumably due to its high reactivity. 3-DG may, on the other hand, pass through the membrane and be detected in the blood.
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| 3. |
- Erixon, Martin, et al.
(författare)
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3,4-dideoxyglucosone-3-ene in peritoneal dialysis fluids infused into the peritoneal cavity cannot be found in plasma.
- 2009
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 29 Suppl 2, s. 28-31
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucose degradation products (GDPs) are important for the outcome of peritoneal dialysis (PD) treatment. The most cytotoxic GDP found in conventionally manufactured fluids, 3,4-dideoxyglucosone-3-ene (3,4-DGE), may in addition be recruited from 3-deoxyglucosone (3-DG). What happens with the GDPs in the fluid infused into patients during PD is not known. We investigated whether 3,4-DGE and 3-DG in PD fluid can be found in plasma during treatment. DESIGN: Patients on PD were dialyzed with a conventional PD fluid containing 43 micromol/L 3,4-DGE and 281 micromol/L 3-DG. Parallel experiments were performed in rats and in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 micromol/L 3,4-DGE and 200 micromol/L 3-DG. RESULTS: The 3,4-DGE concentration in the peritoneum declined at a much higher rate during the dwell than did the 3-DG concentration. However, 3,4-DGE was not detected in the plasma of patients or of rats during dialysis. The 3-DG concentration in plasma peaked shortly after infusion of fluid into the peritoneal cavity. The 3,4-DGE concentration during experimental incubation in plasma declined rapidly; the 3-DG concentration declined only 10% as rapidly (or less). CONCLUSION: During dialysis, 3,4-DGE could not be detected in plasma of either PD patients or rats, presumably because of its high reactivity. On the other hand, 3-DG may pass through the membrane and be detected in the blood.
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| 4. |
- Erixon, Martin
(författare)
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Glucose degradation products in peritoneal dialysis fluids
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients suffering from renal failure must remove extracellular water and waste products from their body in order to survive. One way of doing this is by treatment with peritoneal dialysis (PD). During PD treatment the abdominal cavity is filled and drained continuously with one to three liters of dialysis solution, often containing glucose, which act as an osmotic agent. Glucose creates a pressure gradient over the membrane which forces water and solutes to migrate from the blood into the dialysis fluid. During the production of these fluids, heat sterilization is a must in order to obtain a sterile product. During the heat sterilization glucose degrades to different carbonyl compounds named glucose degradation products (GDPs). GDPs are known to damage the peritoneum, might be responsible for ultrafiltration failure in patients and have a toxic impact on several in vivo systems such as generation of higher plasma advanced glycation end products, stimulation of growth factors (VEGF) and lower dialysate CA 125 levels. GDPs also display higher cytotoxicity in various in vitro systems. As a result, new biocompatible multicompartment PD fluids, low in GDPs, have been produced. The reason for the low concentrations of GDPs in these fluids is mainly a low pH (pH ? 3.1) in the glucose compartment in combination with a high glucose concentration during sterilization. The difference in the concentration of GDPs within and between the new biocompatible and the conventionally manufactured PD fluids is great. This is mainly due to different manufacturing conditions and different sterilization processes. 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most toxic GDP formed in PD fluids. Its toxicity has been confirmed in several in vitro studies, for example in inhibition of growth in cultured cell fibroblasts, retardation of wound healing, downregulation of zonula occludens protein 1 expression in mesothelial cells, inducing apoptosis in leukocytes and in renal tubular epithelial cells and suppressing effects on immune cells. 3,4-DGE exists in a temperature dependent equilibrium with a pool of 3-deoxyglucosone (3-DG) and 3-deoxyaldose-2-ene (3-DA). If stored above room temperature, the equilibrium in the pool changes and the concentration of 3,4-DGE increases, whereas 3-DG decreases (3-DA has not been identified in PD fluids). During storage and transport of conventional PD fluids short temperature impulses may rapidly form high amounts of 3,4-DGE from its pool making the fluid highly cytotoxic. As the temperature drops the concentration only slowly decreases. Therefore it is important to optimize different parameters during the manufacture of such fluids so as to minimize GDP formation, and a further important question concerns the temperatures at which the fluids are stored and transported before patient use.
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| 5. |
- Erixon, Martin, et al.
(författare)
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How to avoid glucose degradation products in peritoneal dialysis fluids
- 2006
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 26:4, s. 490-497
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The formation of glucose degradation products (GDPs) during sterilization of peritoneal dialysis fluids (PDFs) is one of the most important aspects of biocompatibility of glucose-containing PDFs. Producers of PDFs are thus trying to minimize the level of GDPs in their products. 3,4-Dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP in PDFs. It exists in a temperature-dependent equilibrium with a pool of 3-deoxyglucosone (3-DG) and is a precursor in the irreversible formation of 5-hydroxymethyl furaldehyde (5-HMF). The aim of the present study was to investigate how to minimize GDPs in PDFs and how different manufacturers have succeeded in doing so. Design: Glucose solutions at different pHs and concentrations were heat sterilized and 3-DG, 3,4-DGE, 5-HMF, formaldehyde, and acetaldehyde were analyzed. Conventional as well as biocompatible fluids from different manufacturers were analyzed in parallel for GDP concentrations. Results: The concentrations of 3-DG and 3,4-DGE produced during heat sterilization decreased when pH was reduced to about 2. Concentration of 5-HMF decreased when pH was reduced to 2.6. After further decrease to a pH of 2.0, concentration of 5-HMF increased slightly, and below a pH of 2.0 it increased considerably, together with formaldehyde; 3-DG continued to drop and 3,4-DGE remained constant. Inhibition of cell growth was paralleled by 3,4-DGE concentration at pH 2.0-6.0. A high glucose concentration lowered concentrations of 3,4-DGE and 3-DG at pH 5.5 and of 5-HMF at pH 1. At pH 2.2 and 3.2, glucose concentration had a minor effect on the formation of GDPs. All conventional PDFs contained high levels of 3,4-DGE and 3-DG. Concentrations were considerably lower in the biocompatible fluids. However, the concentration of 5-HMF was slightly higher in all the biocompatible fluids. Conclusion: The best way to avoid reactive GDPs is to have a pH between 2.0 and 2.6 during sterilization. If pHs outside this range are used, it becomes more important to have There are large variations in GDPs, both within and between biocompatible and conventionally manufactured PDFs.
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| 6. |
- Erixon, Martin, et al.
(författare)
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PD fluids contain high concentrations of cytotoxic GDPs directly after sterilization
- 2004
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 24:4, s. 392-398
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids are cytotoxic and affect the survival of the peritoneal membrane. One of the most reactive GDPs in PD fluids is 3,4-dideoxyglucosone-3-ene (3,4-DGE). 3,4-DGE has been reported as an intermediate between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl furaldehyde (5-HMF) during degradation of glucose. In PD fluids, 3,4-DGE exists in a temperature-dependent equilibrium with a pool of unidentified substances. The aim of this study was to explore this equilibrium and its temperature dependence during the first months of storage after the sterilization procedure. Methods: GDPs and inhibition of cell growth (ICG) were measured directly after sterilization of the PD fluid and during storage at different temperatures for 60 days. The following GDPs were analyzed: 3-DG, 3,4-DGE, 5-HMF, formaldehyde, acetaldehyde, glyoxal, and methylglyoxal. Results: Immediately after sterilization, the concentration of 3,4-DGE was 125 mumol/L. During the first weeks of storage, it decreased by about 80%. At the same time, the 3-DG concentration increased. None of the other GDPs were significantly affected. Cytotoxicity correlated well with the concentration of 3,4-DGE. When pure 3,4-DGE was substituted for the lost amount of 3,4-DGE after 30 days of storage, the initial ICG was almost completely regained. Conclusions: Heat sterilization of PD fluids promotes the formation of large quantities of 3,4-DGE, rendering the fluid highly cytotoxic. During storage, the main part of 3,4-DGE is reversibly converted in a temperature-dependent manner to a less cytotoxic pool, consisting mainly of 3-DG. Cytotoxicity seems to be dependent exclusively on 3,4-DGE. In order to avoid higher levels of 3,4-DGE concentrations, PD fluids should not be used too soon after sterilization and should not be stored at temperatures above room temperature.
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| 7. |
- Erixon, Martin, et al.
(författare)
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Take care in how you store your PD fluids: Actual temperature determines the balance between reactive and non-reactive GDPs
- 2005
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 25:6, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Objective: During heat sterilization and during prolonged storage, glucose in peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic. It is an intermediate in degradation between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier reported that there seems to be equilibrium between these GDPs in PDF. The aim of the present study was to investigate details of this equilibrium. Methods: Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40 degrees C for 40 days., Conventional and low-GDP fluids were incubated at various temperatures for up to, 3 weeks. Formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance liquid chromatography. Results: Incubation of 100 mu mol/L 3,4-DGE resulted in the production of 36 mu mol/L 3-DG, 4 mu mol/L 5-HMF, and 40 mu mol/L unidentified substances. With the same incubation, 200 mu mol/L 3-DG was converted to 9 mu mol/L 3,4-DGE, 6 mu mol/L 5-HMF, and 14 mu mol/L unidentified substances. By contrast, 100 mu mol/L 5-HMF was uninfluenced by incubation. In a conventional PDF incubated at 60 degrees C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 mu mol/L. When the fluids were returned to room temperature, the concentration decreased but did not reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased and decreased in the same manner as in the conventional fluid but reached a maximum of only 0.8 mu moL/L. Conclusions: Considerable amounts of 3,4-DGE maybe recruited by increases in temperature in conventional PDFs. Lowering the temperature will again reduce the concentration but much more time will be needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3-deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is recruited from its pool of precursors and the difficulty of getting rid of it again, one should be extremely careful with the temperatures conventional PDFs are exposed to.
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