Studying the Effects of New Peritoneal Dialysis Solutions on the Peritoneum

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 87-93
Author(s):  
Chan Tak Mao ◽  
Susan Yung
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Studies ◽  
Degradation Products ◽  
Animal Experiments ◽  
Angiogenic Growth Factors ◽  
Anatomy And Physiology ◽  
Bio Compatibility ◽  
The Impact ◽  
Peritoneal Function

♦ Background Compelling data underscore the bioincompatible nature of glucose-based peritoneal dialysis (PD) solutions and their detrimental effects on peritoneal physiology and morphology. New PD solutions have been formulated to tackle common clinical problems such as inadequate ultrafiltration or malnutrition, and to improve biocompatibility—the latter aimed at preserving the structural and functional integrity of the peritoneum and reducing adverse systemic effects on the patient. ♦ Methods This article reviews the factors in PD fluids that alter normal peritoneal anatomy and physiology, and the data that illustrate approaches to investigating the local and systemic biocompatibility of new PD solutions. ♦ Results Chronic exposure of the peritoneal membrane to glucose-based PD solutions results in denudation of the mesothelium, thickened submesothelium, and hyalinization of the vasculature, often resulting in reduced or lost solute and water clearance. Data from in vitro or animal experiments and clinical studies have shown improved bio-compatibility profiles with new PD solutions that are glucose-free (that is, dialysates with amino acids or icodextrin), bicarbonate-buffered, or compartmentalized during heat sterilization to reduce levels of glucose degradation products. Improved biocompatibility is denoted by reduced induction of proinflammatory, profibrotic, or angiogenic growth factors in mesothelial cells and macrophages, or by less perturbation of leukocyte phagocytic function. ♦ Conclusions Data from in vitro and animal experiments show more favorable biocompatibility profiles with new PD fluids than with glucose-based dialysates. Clinical studies are ongoing to assess the impact of the new PD fluids on peritoneal function, morbidity, and mortality.

Glucose Degradation Products and Peritoneal Membrane Function

2001 ◽  
Vol 21 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Janusz Witowski ◽  
Thorsten O. Bender ◽  
Gerhard M. Gahl ◽  
Ulrich Frei ◽  
Achim Jörres
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Membrane Function ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
And Function ◽  
The Impact ◽  
Dialysis Fluids

Background The bioincompatibility of peritoneal dialysis fluids (PDF) in current use has been partially attributed to the presence of glucose degradation products (GDPs), which are generated during heat sterilization of PDF. Several of the GDPs have been identified and we have recently demonstrated that these GDPs per se may impair the viability and function of human peritoneal mesothelial cells (HPMC) in vitro. It is also possible that GDP-related toxicity is further exacerbated by the milieu of PDF. We review the current literature on GDP and present the results of experiments comparing the impact of heat- and filter-sterilized PDF on the viability and function of HPMC. Methods Peritoneal dialysis fluids with low (1.5%) and high (4.25%) glucose concentrations were laboratory prepared according to the standard formula and sterilized either by heat (H-PDF; 121°C, 0.2 MPa, 20 minutes) or filtration (F-PDF; 0.2 μ). The buildup of GDP was confirmed by UV absorbance at 284 nm. Confluent HPMC monolayers were exposed to these solutions mixed 1:1 with standard M199 culture medium. After 24 hours, cell viability was assessed with the MTT assay, and interleukin-1β–stimulated monocyte chemotactic protein-1 (MCP-1) release with specific immunoassay. Results Exposure of HPMC to H-PDF resulted in a significant decrease in cell viability, with solutions containing 4.25% glucose being more toxic than 1.5% glucose-based PDF (27.4% ± 3.4% and 53.4% ± 11.0% of control values, respectively). In contrast, viability of HPMC exposed to F-PDF was not different from that of control cells. Moreover, treatment with H-PDF impaired the release of MCP-1 from HPMC to a significantly greater degree compared to F-PDF (17.4% and 24.9% difference for low and high glucose PDF, respectively). Conclusions Exposure of HPMC to H-PDF significantly impairs cell viability and the capacity for generating MCP-1 compared to F-PDF. This effect is likely to be mediated by GDPs present in H-PDF but not in F-PDF.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

Development of Toxic Degradation Products during Heat Sterilization of Glucose-Containing Fluids for Peritoneal Dialysis: Influence of Time and Temperature

1995 ◽  
Vol 15 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Per Kjellstrand ◽  
Evi Martinson ◽  
Anders Wieslander ◽  
Björn Holmquist
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Solution ◽  
Degradation Products ◽  
General Pattern ◽  
Low Ph ◽  
Uv Absorbance ◽  
Influence Of Temperature ◽  
In Vitro Systems

Objective Fluids for peritoneal dialysis (PD) cause cytotoxic reactions in many different in vitro systems. The low pH, the high osmolality of the fluids, and the glucose degradation products formed during heat sterilization have been considered responsible. In the present study, we investigate the influence of temperature and time during heat sterilization of PD fluids and glucose solutions on glucose degradation and cytotoxicity of the solutions. Design Ampoules containing PD-fluid or glucose solution were heated in an oil bath to predetermined F o values (combinations of time and temperature giving equal energy/bacteriallethality). Cytotoxicity of the solutions was measured as groWth inhibition of cultured L-929 fibroblasts. Glucose degradation was measured as UV absorbance at 228 and 284 nm. Results The same general pattern was seen in both PD fluid and glucose solution. Cytotoxicity decreased from 90% to 15% when the sterilization temperature was increased from 115° to 140°C and concomitantly the length of time shortened in order to maintain equal bacteriallethality. Under the same conditions, degradation products, measured as UV absorbance at 284 nm, decreased from 0.2 to 0.02. Conclusion To minimizethe development of cytotoxic breakdown products, high temperatures over short periods of time should be used to heat-sterilize PD fluids. Even as small an increase as 5°C at around 120°C will improve the quality of the solutions.

Peritoneal Dialysis Solutions Low in Glucose Degradation Products—evidence for Clinical Benefits

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 123-127
Author(s):  
Tadashi Tomo
Keyword(s):  
Peritoneal Dialysis ◽  
Vascular Function ◽  
Degradation Products ◽  
Peritoneal Mesothelial Cells ◽  
Advanced Glycosylation End Products ◽  
Glucose Degradation Products ◽  
Peritoneal Dialysis Fluid ◽  
Clinical Benefits ◽  
Human Peritoneal Mesothelial Cells ◽  
Peritoneal Function

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has bio-compatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.

L-2-Oxothiazolidine-4-Carboxylate: An Agent that Modulates Lipopolysaccharide-Induced Peritonitis in Rats

2002 ◽  
Vol 22 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Katarzyna Korybalska ◽  
Katarzyna Wieczorowska–Tobis ◽  
Alicja Polubinska ◽  
Justyna Wisniewska ◽  
James Moberly ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cell ◽  
Cellular Damage ◽  
Dialysis Fluid ◽  
Acute Peritonitis ◽  
Cell Counts ◽  
Dialysis Solution ◽  
Peritoneal Leukocytes ◽  
Peritoneal Function

Objective L-2-Oxothiazolidine-4-carboxylate (OTZ), a cysteine precursor, is a substrate for intracellular glutathione synthesis. As shown previously, OTZ prevents free-radical induced cellular damage during in vitro simulation of peritoneal dialysis. In the present study, we examined the effect of adding OTZ to peritoneal dialysis solution on peritoneal function and structure during lipopolysaccharide (LPS)-induced peritonitis in rats. In addition, we studied the effects of pretreatment with OTZ (given orally) on the effects of LPS-induced peritonitis in rats. Methods Peritonitis was induced in rats by adding LPS (5 μg/mL) to the dialysis fluid. For acute experiments, rats were exposed to a single infusion of dialysis solution containing LPS or to LPS plus 5 mmol/L OTZ; peritoneal cell counts and permeability were determined after 4 hours. Alternatively, rats were pretreated with OTZ added to the drinking water (0.1%) for 10 days prior to infusion of LPS. For chronic experiments, peritoneal dialysis was performed over a 3-week period in rats with implanted peritoneal catheters. On days 8, 9, and 10 of the experiment, the rats were infused intraperitoneally with solution containing LPS (5 μg/mL), or LPS plus 5 mmol/L OTZ, to induce acute peritonitis. At the end of dialysis (10 days after the episodes of peritonitis), peritoneal function was assessed using a peritoneal equilibration test (PET), and peritoneal biopsies were taken to assess effects on peritoneal morphology. Results In the acute experiments, exposure to LPS led to increased peritoneal cell counts (+61% vs control, p < 0.05) and enhanced permeability of the peritoneum, leading to a loss in ultrafiltration (–63%, p < 0.0005). The glutathione concentration in peritoneal leukocytes also decreased during acute peritonitis (–31%, p < 0.05). During LPS-induced peritonitis, OTZ prevented the increase in dialysate cell count and the decrease in cellular glutathione content. Simultaneous administration of OTZ did not prevent the increased peritoneal permeability induced by LPS. However, in rats pretreated with OTZ, LPS-induced permeability to protein was significantly lower than in the nontreated animals (0.049 ± 0.011 vs 0.087 ± 0.034, p < 0.05). In the chronic experiments, LPS-induced peritonitis did not lead to any functional differences in peritoneal transport at the end of 3 weeks of dialysis. However, LPS-induced peritonitis led to increased thickness of the peritoneum and neovascularization within peritoneal interstitium compared to peritonitis-free animals. In contrast to the LPS-treated animals, the peritoneum of the rats exposed to LPS in the presence of OTZ was of a thickness similar to that in the control rats. Conclusion Supplementation of dialysis fluid with OTZ prevented changes in cellular glutathione levels and dialysate cell counts during acute peritonitis in rats. During chronic dialysis in rats exposed to intermittent peritonitis episodes, OTZ prevented increased thickening and neovascularization of the peritoneum. Our results suggest this may help to protect the peritoneal membrane during episodes of peritonitis.

scholarly journals The Impact of Uremic Toxins on Cerebrovascular and Cognitive Disorders

Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 303 ◽  
Author(s):  
Maryam Assem ◽  
Mathilde Lando ◽  
Maria Grissi ◽  
Saïd Kamel ◽  
Ziad Massy ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Cognitive Disorders ◽  
Neurological Complications ◽  
Cerebrovascular Diseases ◽  
Uremic Toxins ◽  
Current Evidence ◽  
Cognitive Disorders And Dementia ◽  
The Impact

Individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia. Stroke is also highly prevalent in this population and is associated with a higher risk of neurological deterioration, in-hospital mortality, and poor functional outcomes. Evidence from in vitro studies and in vivo animal experiments suggests that accumulation of uremic toxins may contribute to the pathogenesis of stroke and amplify vascular damage, leading to cognitive disorders and dementia. This review summarizes current evidence on the mechanisms by which uremic toxins may favour the occurrence of cerebrovascular diseases and neurological complications in CKD.

Glucose Degradation Products and the Peritoneal Mesothelium

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 19-22 ◽  
Author(s):  
Achim Jörres ◽  
Thorsten O. Bender ◽  
Janusz Witowski
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Experimental Models ◽  
Buffer System ◽  
Peritoneal Fibrosis ◽  
High Concentration ◽  
Peritoneal Mesothelial Cells ◽  
Cell Functions ◽  
Glucose Degradation Products

Conventional heat-sterilized, glucose-based peritoneal dialysis (PD) fluids contain significant amounts of glucose degradation products (GDPs) such as aldehydes and dicarbonyl compounds (glyoxal, methylglyoxal). These GDPs have been shown to impair cell functions in various in vitro experimental models. In peritoneal mesothelial cells, GDPs dose-dependently inhibit cell proliferation and mediator synthesis. In addition, some GDPs potently promote generation of advanced glycation end-products (AGEs). Immunohistochemistry finds AGEs in the peritoneal membrane of chronic continuous ambulatory peritoneal dialysis (CAPD) patients, suggesting that peritoneal AGE accumulation may be involved in chronic peritoneal fibrosis. The formation of GDPs might be prevented by filter-sterilization of PD fluids. Another option is to separate the glucose and the buffer system in dual-chambered or multi-chambered containers. In these systems, the glucose is kept in a separate compartment at high concentration and very low pH—both conditions being known to minimize the degree of glucose decomposition during autoclaving. Initial experimental evidence suggests that these novel, multi-chambered fluids significantly improve in vitro biocompatibility; however, the clinical relevance of these results remains to be established in clinical trials.

In Vitro Biocompatibility of a Heat -Sterilized, Low Toxic, and Less Acidic Fluid for Peritoneal Dialysis

1995 ◽  
Vol 15 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Anders P. Wieslander ◽  
Reinhold Deppisch ◽  
Eva Svensson ◽  
Gunita Forsbäck ◽  
Rose Speidel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Performance ◽  
Mononuclear Cells ◽  
Degradation Products ◽  
Fibroblast Cell ◽  
Interleukin 1Β ◽  
Uv Absorbance ◽  
Glucose Degradation Products ◽  
In Vitro Biocompatibility

Objective The aim of this study was to investigate a peritoneal dialysis (PD) fluid (PD-Bio), produced with the intention of reducing the amount of glucose degradation products and to increase the final pH. The heat sterilization of the fluid was performed with the glucose separated from the electrolytes. After sterilization the two solutions were combined. Methods The in vitro biocompatibility of PD-Bio was measured as the inhibition of cell growth of a cultured fibroblast cell line and as the stimulated release of interleukin-1β from cultured human mononuclear cells. The glucose degradation products were measured as UV absorbance at 228 nm or 284 nm and the concentration of aldehydes was estimated with high-performance liquid chromatography and gas chromatography. Results Our results demonstrate that in comparison to conventional PD fluids the pH of PD-Bio was increased, to about 6.5. Due to less contaminating glucose degradation products in PD-Bio, basal cytotoxicity was significantly decreased for both 1.5% and 4% glucose-containing fluids, and the stimulated release of interleukin-1β was normalized compared to sterile filtered controls with the same pH. UV absorbance measured at 228 nm was decreased, whereas the absorbance at 284 nm was equal to that of a conventional fluid. In PD-Bio the concentrations of formaldehyde, acetaldehyde, methylglyoxal, and 2-furaldehyde were found to be below the detection limit, whereas glyoxal was present in the same and 5hydroxymethylfurfural (5-HMF) in higher concentrations than in conventionally produced PD fluid. Conclusions The results demonstrate that it is possible to improve biocompatibility of PD fluids by simply changing the way the fluid is produced.

Peritoneal Injury by Methylglyoxal in Peritoneal Dialysis

2006 ◽  
Vol 26 (3) ◽  
pp. 380-392 ◽  
Author(s):  
Ichiro Hirahara ◽  
Eiji Kusano ◽  
Satoru Yanagiba ◽  
Yukio Miyata ◽  
Yasuhiro Ando ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Basement Membrane ◽  
Structural Changes ◽  
Type Iv Collagen ◽  
Degradation Products ◽  
Abdominal Cocoon ◽  
Type Iv ◽  
Type Iv Collagen 7S ◽  
Peritoneal Function

Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats ( n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.

scholarly journals Impact of Glucosinolate Content in Broccoli (Brassica oleracea (Italica Group)) on Growth of Pseudomonas marginalis, a Causal Agent of Bacterial Soft Rot

Plant Disease ◽  
2002 ◽  
Vol 86 (6) ◽  
pp. 629-632 ◽  
Author(s):  
Craig S. Charron ◽  
Carl E. Sams ◽  
Craig H. Canaday
Keyword(s):  
Brassica Oleracea ◽  
Degradation Products ◽  
Linear Regression Analysis ◽  
Soft Rot ◽  
Causal Agent ◽  
Glucosinolate Content ◽  
Bacterial Soft Rot ◽  
Vitro Assay ◽  
The Impact

Glucosinolate degradation products are known to suppress microbes. Brassica species produce glucosinolates. Previous investigations determined that susceptibility to bacterial soft rot of broccoli (Brassica oleracea (Italica group)) varied significantly by cultivar. To evaluate the impact of glucosinolates on Pseudomonas marginalis, a causal agent of bacterial soft rot, glucosinolates were measured in lyophilized florets from broccoli ‘Arcadia’, ‘Emperor’, ‘Green Comet’, ‘Green Valiant’, ‘Marathon’, ‘Packman’, ‘Premium Crop’, and ‘Shogun’. Total glucosinolate content was highest in ‘Shogun’ (29.8 μmol/g) and lowest in ‘Emperor’ (0.5 μmol/g). In an in vitro assay, simple linear regression analysis showed that 48% of differences in suppression of P. marginalis growth could be explained by differences in total glucosinolate content (P ≤ 0.01). Plant breeding efforts should include glucosinolate levels as a factor in selecting for disease resistance.

Sign in / Sign up

Export Citation Format

Share Document