PD Fluids Contain High Concentrations of Cytotoxic GDPs Directly after Sterilization

2004 ◽  
Vol 24 (4) ◽  
pp. 392-398 ◽  
Author(s):  
Martin Erixon ◽  
Torbjörn Lindén ◽  
Per Kjellstrand ◽  
Ola Carlsson ◽  
Malin Ernebrant ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Main Part ◽  
Room Temperature ◽  
Degradation Products ◽  
The Other ◽  
Dependent Manner ◽  
Peritoneal Membrane ◽  
Temperature Dependent ◽  
Different Temperatures ◽  
High Concentrations

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 μmol/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.

Biocompatibility of New Peritoneal Dialysis Solutions: Clinical Experience

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 48-56 ◽  
Author(s):  
Elvia Garcia–Lopez ◽  
Bengt Lindholm ◽  
Anders Tranæus
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Experience ◽  
Degradation Products ◽  
Peritoneal Membrane ◽  
Negative Effects ◽  
New Era ◽  
Combined Use ◽  
Osmotic Agent ◽  
High Concentrations ◽  
Conventional Solution

The successful development of peritoneal dialysis (PD) during the last two decades has been made possible by using well-established glucose-based solutions with lactate as buffer. On the other hand, awareness has been increasing about the potentially negative effects of the high concentrations of glucose and lactate, and the low pH of conventional PD solutions. This awareness has prompted an intensive effort to search for and test alternative solutions. As a result, three new, more biocompatible solutions— containing either less glucose or less lactate—are available. Amino acid–based solution uses amino acids instead of glucose as the osmotic agent; it is indicated for treatment of malnutrition. The higher pH and absence of glucose in this solution may prevent alterations of the peritoneal membrane caused by acidity and high glucose concentrations. Bicarbonate/lactate–buffered solution contains a physiologic concentration of bicarbonate and a reduced concentration of lactate; it also has a physiologic pH and markedly reduced levels of glucose degradation products (GDPs). Icodextrin-based solution contains icodextrin as the osmotic agent; it is indicated for long dwells, delivering sustained ultrafiltration for more than 16 hours. This iso-osmolar glucose-free solution may reduce peritoneal membrane alterations caused by glucose or the hyperosmolality (or both) of conventional solutions. Clinical experience of the new solutions is now extensive, and their efficacy and safety are well documented. It therefore seems appropriate to state that we have entered a new era of PD therapy. Each of the new solutions may be less damaging to the peritoneal membrane than conventional solution. In addition, they permit better management of malnutrition and fluid status, and may thus help to improve PD patient survival. Although the effects of each of these new solutions have been well described, clinical documentation of the combined use of these new biocompatible PD solutions is still insufficient. However, the results of studies are expected, during the coming years, to support the combined use of the new solutions as the preferred standard practice for PD.

scholarly journals Sarin and Air Permeation Through a Nanoporous Graphene

MRS Advances ◽  
2020 ◽  
Vol 5 (27-28) ◽  
pp. 1475-1482
Author(s):  
Marco A. Maria ◽  
Alexandre F. Fonseca
Keyword(s):  
Room Temperature ◽  
Initial Pressure ◽  
Chemical Warfare Agent ◽  
The Other ◽  
Graphene Nanosheet ◽  
Different Temperatures ◽  
Nanoporous Graphene ◽  
Dynamics Simulations ◽  
And Storage ◽  
Air Permeation

ABSTRACTSarin gas is a dangerous chemical warfare agent (CWA). It is a nerve agent capable of bringing a person to death in about 15 minutes. A lethal concentration of sarin molecules in air is about 30 mg/m3. Experimental research on this gas requires very careful safety protocols for handling and storage. Therefore, theoretical and computational studies on sarin gas are very welcome and might provide important safe guides towards the management of this lethal substance. In this work, we investigated the interactions between sarin, air and nanoporous graphene, using tools of classical molecular dynamics simulations. Aiming to cast some light in the possible sarin selective filtration by graphene, we designed a bipartite simulation box with a porous graphene nanosheet placed at the middle. Sarin and air molecules were initially placed only on one side of the box so as to create an initial pressure towards the passage of both to the other side. The box dimensions were chosen so that the hole in the graphene was the only possible way through which sarin and air molecules can get to the other side of the box. The number of molecules that passed through the hole in graphene was monitored during 10 ns of simulation and the results for different temperatures were compared. The results show that, as far as the size of the holes are small, van der Waals forces between graphene and the molecules play a significant role on keeping sarin near graphene, at room temperature.

Biological Significance of Reducing Glucose Degradation Products in Peritoneal Dialysis Fluids

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
Anders Wieslander ◽  
Torbjörn Linden ◽  
Barbara Musi ◽  
Ola Carlsson ◽  
Reinhold Deppisch
Keyword(s):  
Peritoneal Dialysis ◽  
Side Effects ◽  
Host Defense ◽  
Degradation Products ◽  
Biological Significance ◽  
Peritoneal Membrane ◽  
Negative Side ◽  
Glucose Degradation Products ◽  
Negative Side Effects

Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds—such as formaldehyde and 3-deoxyglucosone—have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. Conclusion Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.

scholarly journals Effect ofbalanceSolution on the Peritoneal Membrane in Automated Peritoneal Dialysis

2016 ◽  
Vol 36 (5) ◽  
pp. 569-572 ◽  
Author(s):  
Tatiana De los Ríos ◽  
Juan Pérez-Martínez ◽  
Jose Portoles ◽  
Monika Lichodziejewska-Niemierko ◽  
Maite Rivera ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Peritoneal Membrane ◽  
Open Label ◽  
Cell Functions ◽  
Neutral Ph ◽  
Appearance Rate ◽  
Glycation End Products ◽  
Membrane Cell

Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end-products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross-over phase IV study compared the in vivo biocompatibility of a neutral-pH, low-GDP peritoneal dialysis (PD) solution ( balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution.

3,4-DGE in Peritoneal Dialysis Fluids Cannot be Found in Plasma after Infusion into the Peritoneal Cavity

2008 ◽  
Vol 28 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Martin Erixon ◽  
Anders Wieslander ◽  
Torbjörn Lindén ◽  
Ola Carlsson ◽  
Jan Åke Jönsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Human Plasma ◽  
Peritoneal Cavity ◽  
Degradation Products ◽  
High Reactivity ◽  
The Other ◽  
Glucose Degradation Products ◽  
Pass Through ◽  
Dialysis Fluids

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 μmol/L 3,4-DGE and 281 μmol/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 μmol/L 3,4-DGE and 200 μmol/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.

scholarly journals Stability of the Combination of Ceftazidime and Cephazolin in Icodextrin or PH Neutral Peritoneal Dialysis Solution

2014 ◽  
Vol 34 (2) ◽  
pp. 212-218 ◽  
Author(s):  
Rahul P. Patel ◽  
Madhur D. Shastri ◽  
Mohammad Bakkari ◽  
Troy Wanandy ◽  
Matthew D. Jose
Keyword(s):  
Peritoneal Dialysis ◽  
Body Temperature ◽  
High Performance ◽  
Room Temperature ◽  
Storage Conditions ◽  
Initial Concentration ◽  
Dialysis Solution ◽  
Different Temperatures ◽  
Colour Changes ◽  
The Stability

IntroductionThe objective of this study was to investigate the stability of ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral peritoneal dialysis (PD) solution.MethodsCeftazidime and cephazolin were injected into either a 7.5% icodextrin or pH neutral PD bag to obtain the concentration of 125 mg/L of each antibiotic. A total of nine 7.5% icodextrin or pH neutral PD bags containing ceftazidime and cephazolin were prepared and stored at 1 of 3 different temperatures: 4°C in a domestic refrigerator; 25°C at room temperature; or 37°C (body temperature) in an incubator. An aliquot was withdrawn immediately before (0 hour) or after 12, 24, 48, 96, 120, 144, 168 and 336 hours of storage. Each sample was analyzed in duplicate for the concentration of ceftazidime and cephazolin using a stability-indicating high-performance liquid chromatography technique. Ceftazidime and cephazolin were considered stable if they retained more than 90% of their initial concentration. Samples were also assessed for pH, colour changes and evidence of precipitation immediately after preparation and on each day of analysis.ResultsCeftazidime and cephazolin in both types of PD solution retained more than 90% of their initial concentration for 168 and 336 hours respectively when stored at 4°C. Both of the antibiotics lost more than 10% of the initial concentration after 24 hours of storage at 25 or 37°C. There was no evidence of precipitation at any time under the tested storage conditions. Change in the pH and color was observed at 25 and 37°C, but not at 4°C.ConclusionPremixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. This allows the preparation of PD bags in advance, avoiding the necessity for daily preparation. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and pre-warming of PD bags to body temperature prior to its administration.

scholarly journals The Effect of Far-Infrared Therapy on the Peritoneal Membrane Transport Characteristics of Uremic Patients Undergoing Peritoneal Dialysis: An Open-Prospective Proof-of-Concept Study

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 669
Author(s):  
Ching-Po Li ◽  
Chyong-Mei Chen ◽  
Chia-Hao Chan ◽  
Szu-Yuan Li ◽  
Ming-Tsun Tsai ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Membrane Transport ◽  
Degradation Products ◽  
Far Infrared ◽  
Proof Of Concept ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Glucose Degradation Products ◽  
Average Status

Long-term peritoneal dialysis (PD) can lead to detrimental changes in peritoneal membrane function, which may be related to the accumulation of glucose degradation products. A previous study demonstrated that 6 months of far-infrared (FIR) therapy may decrease glucose degradation products in PD dialysate. Due to limited literature on this matter, this study aims to investigate the effect of FIR therapy on the peritoneal membrane transport characteristics of PD patients. Patients were grouped according to baseline peritoneal transport status: lower transporters (low and low-average) and higher transporters (high-average and high). Both groups underwent 40 min of FIR therapy twice daily for 1 year. In lower transporters, FIR therapy increased weekly dialysate creatinine clearance (6.91 L/wk/1.73 m2; p = 0.04) and D/P creatinine (0.05; p = 0.01). In higher transporters, FIR therapy decreased D/P creatinine (−0.05; p = 0.01) and increased D/D0 glucose (0.05; p = 0.006). Fifty percent of high transporter patients shifted to high-average status after FIR therapy. FIR therapy may decrease D/P creatinine for patients in the higher transporter group and cause high transporters to shift to high-average status, which suggests the potential of FIR therapy in improving peritoneal membrane function in PD patients.

Expression of Aquaporin-1 in Human Peritoneal Mesothelial Cells and Its Upregulation by GlucoseIn Vitro

2001 ◽  
Vol 12 (5) ◽  
pp. 1036-1045 ◽  
Author(s):  
KAR NENG LAI ◽  
FU KEUNG LI ◽  
HAO YUI LAN ◽  
SYDNEY TANG ◽  
ANITA W. L. TSANG ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peritoneal Dialysis ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Membrane ◽  
Dialysis Adequacy ◽  
Peritoneal Mesothelial Cells ◽  
Aqp1 Expression ◽  
Human Peritoneal Mesothelial Cells ◽  
Osmotic Agents

Abstract. Aquaporin (AQP) is a family of water channels that are highly selective for the passage of water and occasionally glycerol. In previous studies, only AQP1 was found in human peritoneal endothelial cells in both control subjects and patients on peritoneal dialysis. As human peritoneal mesothelial cells (HPMC) play an important role in dialysis adequacy and fluid balance in continuous ambulatory peritoneal dialysis patients, this study examined whether AQP1 is present in HPMC. It was found that AQP1 mRNA and protein are present in HPMC constitutively. The localization of AQP1 protein in peritoneal mesothelial cells was confirmed by double immunohistochemical staining of the mesothelial lining of human peritoneal membrane. More important, the expression of AQP1 in HPMC is not constitutive and the transcription and biosynthesis of AQP1 in HPMC is inducible by osmotic agents such as glucose and mannitol. There was significant enhancement of AQP1 biosynthesis upon exposure to glucose in a time- and dose-dependent manner (P< 0.0001). Similar findings were observed in the AQP1 biosynthesis by an endothelial cell line, EA.hy 926. Of particular interest, the upregulation in AQP1 mRNA or biosynthesis in mesothelial cells was always significantly higher than that of endothelial cells when the experiments were conducted under identical settings (P< 0.001). AQP1 expression in HPMC was demonstrated for the first time. Osmotic agents upregulate both mRNA and protein expression of this aquaporin. The role of AQP1 in HPMC in maintaining the ultrafiltration of the peritoneal membrane is potentially of clinical interest.

Take Care in how you Store Your PD Fluids: Actual Temperature Determines the Balance between Reactive and Non-Reactive GDPs

2005 ◽  
Vol 25 (6) ◽  
pp. 583-590 ◽  
Author(s):  
Martin Erixon ◽  
Anders Wieslander ◽  
Torbjörn Lindén ◽  
Ola Carlsson ◽  
Gunita Forsbäck ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Peritoneal Dialysis ◽  
Aqueous Solutions ◽  
Carbonyl Compounds ◽  
High Performance ◽  
Room Temperature ◽  
Degradation Products ◽  
Prolonged Storage ◽  
Dialysis Fluids

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°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 μmol/L 3,4-DGE resulted in the production of 36 μmol/L 3-DG, 4 μmol/L 5-HMF, and 40 μmol/L unidentified substances. With the same incubation, 200 μmol/L 3-DG was converted to 9 μmol/L 3,4-DGE, 6 μmol/L 5-HMF, and 14 μmol/L unidentified substances. By contrast, 100 μmol/L 5-HMF was uninfluenced by incubation. In a conventional PDF incubated at 60°C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 μmol/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 μmol/L. Conclusions Considerable amounts of 3,4-DGE may be 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.

Is Free Thyroxine Accurately Measurable at Room Temperature?

1992 ◽  
Vol 38 (6) ◽  
pp. 880-886 ◽  
Author(s):  
H A Ross ◽  
T J Benraad
Keyword(s):  
Temperature Effect ◽  
Room Temperature ◽  
Free Thyroxine ◽  
The Other ◽  
Temperature Dependent ◽  
Thyroxine Binding Globulin ◽  
Total Binding ◽  
Relative Contribution ◽  
Back Titration ◽  
Titration Assay

Abstract Two recently developed two-step, or "back-titration" assay kits for free thyroxine (FT4)--one based on a europium-labeled derivative of T4, the other on conventional radiolabeled T4--were compared with both symmetrical dialysis and an indirect FT4 radioimmunoassay. Discrepancies between the two-step and the other two methods were observed, particularly in samples that had very low to zero thyroxine-binding globulin (TBG) content. In those instances the two-step methods gave values almost twice as high as the other methods. This effect could be largely reversed in one of the two-step assays and completely reversed in the other by performing the first incubation step at 37 degrees C rather than at room temperature, as prescribed by the manufacturers. When symmetrical dialysis is performed at both temperatures, FT4 at room temperature is about 40% of the amount determined at 37 degrees C, except in zero-TBG samples, where it averages almost 80% of the value at 37 degrees C. Moreover, we demonstrated that the affinity of TBG for T4 is much more temperature-dependent than the affinity of transthyretin and albumin for T4, so that the net temperature effect on the FT4 in a sample depends on the relative contribution of TBG to total binding. We conclude that performing FT4 assays at room temperature is principally incorrect and leads to falsely increased values when samples with very low TBG concentrations are analyzed.

Sign in / Sign up

Export Citation Format

Share Document