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 Peritoneal Dialysis Fluid Supplementation with Alanyl-Glutamine Attenuates Conventional Dialysis Fluid-Mediated Endothelial Cell Injury by Restoring Perturbed Cytoprotective Responses

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1678
Author(s):  
Rebecca Herzog ◽  
Maria Bartosova ◽  
Silvia Tarantino ◽  
Anja Wagner ◽  
Markus Unterwurzacher ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peritoneal Dialysis ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Cellular Damage ◽  
Vascular Pathology ◽  
Vascular Changes ◽  
Dialysis Fluid ◽  
Peritoneal Dialysis Fluid

Long-term clinical outcome of peritoneal dialysis (PD) depends on adequate removal of small solutes and water. The peritoneal endothelium represents the key barrier and peritoneal transport dysfunction is associated with vascular changes. Alanyl-glutamine (AlaGln) has been shown to counteract PD-induced deteriorations but the effect on vascular changes has not yet been elucidated. Using multiplexed proteomic and bioinformatic analyses we investigated the molecular mechanisms of vascular pathology in-vitro (primary human umbilical vein endothelial cells, HUVEC) and ex-vivo (arterioles of patients undergoing PD) following exposure to PD-fluid. An overlap of 1813 proteins (40%) of over 3100 proteins was identified in both sample types. PD-fluid treatment significantly altered 378 in endothelial cells and 192 in arterioles. The HUVEC proteome resembles the arteriolar proteome with expected sample specific differences of mainly immune system processes only present in arterioles and extracellular region proteins primarily found in HUVEC. AlaGln-addition to PD-fluid revealed 359 differentially abundant proteins and restored the molecular process landscape altered by PD fluid. This study provides evidence on validity and inherent limitations of studying endothelial pathomechanisms in-vitro compared to vascular ex-vivo findings. AlaGln could reduce PD-associated vasculopathy by reducing endothelial cellular damage, restoring perturbed abundances of pathologically important proteins and enriching protective processes.

Effect of N-Acetylglucosamine on Function of Peritoneal Leukocytes

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 365-369 ◽  
Author(s):  
Malgorzata Kuzlan-Pawlaczyk ◽  
Krzysztof Pawlaczyk ◽  
Katarzyna Wieczorowska Tobis ◽  
Alicja Polubinska ◽  
Justyna Wisniewska ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Count ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Differential Cell Count ◽  
Dialysis Solution ◽  
Peritoneal Leukocytes ◽  
Factor Α

Objective To compare effects of N-acetylglucosamine (NAG) -based and glucose-based dialysis fluids on the function of peritoneal leukocytes in conditions of peritoneal dialysis. Design In vitro experiments on ex vivo isolated rat peritonealleukocytes. Materials Peritoneal leukocytes were isolated from rats on chronic peritoneal dialysis. On alternate days, fluid exchanges were performed with NAG-based or glucosebased dialysis solutions. After a 4-hour dwell, dialysate was drained and peritoneal leukocytes were incubated in vitro :I= lipopolysaccharide (LPS). Production of nitrites (index of NO synthesis), tumor necrosis factor α (TNFα), interleukin-1 β (IL -1 β), and interferon gamma (IFN-y) by unstimulated or stimulated peritoneal leukocytes originating from NAG-based or glucose-based fluid was measured. Results Dialysate cell count was lower during exchanges with NAG-based fluid (2113 :I= 615 cells/μL) as compared to glucose-based fluid (3643 :I= 1108 cells/μL; p < 0.01). Differential cell count was similar in both studied groups. Unstimulated peritoneal leukocytes from NAGbased dialysate produced more NO (nitrites) (0.65 ± 0.07 μmol per 106 cells) than did cells from glucose-based dialysate (0.26 :I= 0.09 μmol per 106 cells, p < 0.01). Stimulated peritoneal leukocytes from NAG-based dialysate produced more cytokines than did cells from glucose-based dialysate: TNFα, 135.2 ± 37.0 pg versus 70.2 :I= 21.8 pg per 106 cells respectively, p < 0.01; IL -1 β, 143.2 :I= 60.9 pg versus 99.1 :I= 22.4 pg per 106 cells respectively, p < 0.05; IFN-y, 16.2:1= 12.5 pg versus 6.0:1= 1.8 pg per 106 cells respectively, p <0.01. Conclusions We demonstrated that rat peritonealleukocytes exposed in vivoto NAG-based dialysis fluid have better ability to produce inflammatory mediators than do peritoneal leukocytes from the same donor, but exposed in vivo to glucose-based dialysis solution.

The Effect of a Nitric Oxide Inhibitor (L-Name) on Peritoneal Transport during Dialysis in Rats

1998 ◽  
Vol 18 (2) ◽  
pp. 188-192 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Katarzyna Wieczorowska Tobis ◽  
Katarzyna Korybalska ◽  
Alicja Polubinska ◽  
Maciej Radkowski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Peritoneal Dialysis ◽  
Significant Decline ◽  
Nitric Oxide Synthesis ◽  
Dialysis Fluid ◽  
Large Molecules ◽  
Acute Peritonitis ◽  
Important Mediator ◽  
Peritoneal Transport ◽  
Nitric Oxide Inhibitor

Objective To assess the effect of an inhibitor of nitric oxide synthesis [NG-nitro-L-arginine methyl ester (L-NAME)] on peritoneal transport during peritoneal dialysis (PD) and peritonitis in rats. Methods The authors studied peritoneal transport of small and large solutes, and net ultrafiltration (UF) in rats during PD with Dianeal 3.86 (Baxter, McGaw Park, IL, U.S.A.). They evaluated the effect of L-NAME used as an additive to dialysis fluid in concentrations 0.5 -5 mg/m L on peritoneal transport of small and large molecules and on transperitoneal UF. In addition, they studied the effect of L-NAME (5 mg/mL) during acute peritonitis induced by lipopolysaccharides (5 μg/mL) given intraperitoneally. Results The addition of L-NAME to dialysis fluid increased the selectivity of the peritoneum and net UF during dialysis. Lipopolysaccharides used as an additive to the dialysis fluid, together with L-NAME, did not induce changes in transperitoneal transport of small and large solutes and did not cause a significant decline in net UF. L-NAME given intraperitoneally reduced both local and systemic production of nitric oxide, which might explain its effects on peritoneal transport. Conclusions Nitric oxide is an important mediator of changes in peritoneal transport and its effect is especially significant during peritonitis.

scholarly journals Valsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling

2020 ◽  
Vol 245 (11) ◽  
pp. 983-993 ◽  
Author(s):  
Jing Liu ◽  
Yuan Feng ◽  
Cheng Sun ◽  
Wei Zhu ◽  
Qing-Yan Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peritoneal Dialysis ◽  
Protein Expression ◽  
High Glucose ◽  
Collagen I ◽  
Peritoneal Fibrosis ◽  
Dialysis Solution ◽  
Mtorc1 Pathway ◽  
Peritoneal Dialysis Solution

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway. Impact statement Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.

scholarly journals In Vitro Evaluation of the Activities of Telavancin, Cefazolin, and Vancomycin against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Peritoneal Dialysate

2007 ◽  
Vol 51 (12) ◽  
pp. 4521-4524 ◽  
Author(s):  
Frances L. Clouse ◽  
Laurie B. Hovde ◽  
John C. Rotschafer
Keyword(s):  
Staphylococcus Aureus ◽  
Peritoneal Dialysis ◽  
In Vitro Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Dialysis Fluid ◽  
Methicillin Resistant ◽  
Peritoneal Dialysate ◽  
Peritoneal Dialysis Fluid ◽  
Vitro Model

ABSTRACT This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

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.

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.

How to Increase Adequacy of Peritoneal Dialysis in Children?

2005 ◽  
Vol 25 (3_suppl) ◽  
pp. 135-136
Author(s):  
Cornelis H. Schröder
Keyword(s):  
Peritoneal Dialysis ◽  
Surface Area ◽  
Body Surface ◽  
Glucose Concentration ◽  
Peritoneal Membrane ◽  
Dialysis Fluid ◽  
Peritoneal Equilibration Test ◽  
Dialysis Adequacy ◽  
Intraperitoneal Pressure ◽  
Dialysis Solution

Since children on dialysis are treated most often with nightly intermittent peritoneal dialysis, adequacy of dialysis is determined by the number and duration of cycles, the volume of the dialysis fluid applied, and the choice of dialysis solution. The number and duration of cycles are dependent on the maximal acceptable duration of night rest and the permeability properties of the peritoneal membrane. The latter can be established by performance of a peritoneal equilibration test. The volume used should be about 1200 mL/m2 body surface area, and intraperitoneal pressure should be between 5 and 15 cm H2O. The dialysis solution administered should have a glucose concentration as low as possible, and an icodextrin daytime dwell may be considered.

Compatibility of Cephalosporins and Aminogl Ycosides in Peritoneal Dialysis Fluid

1983 ◽  
Vol 3 (3) ◽  
pp. 128-129 ◽  
Author(s):  
Carol Loeppky ◽  
Eugene Tarka ◽  
E. Dale Everett
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Peritoneal Dialysis ◽  
In Vitro Studies ◽  
Dialysis Fluid ◽  
Peritoneal Dialysis Fluid ◽  
The Individual ◽  
And Staphylococcus Aureus

Often dialysis -associated peritonitis is treated before the results of cultures are known with a cephalosporin and an aminoglycoside in combination. Because there may be antagonism between the individual drugs in such combinations, we have investigated this possibility through the use of timed, killing curves in dialysate effluent. We tested various cephalosporins and aminoglycosides alone and in combination at concentrations usually instilled into the peritoneum and determined their activity against one strain each of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The results of these in-vitro studies show no evidence of antagonism but rather suggest an additive effect as evidenced by more rapid killing.

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